JAJournal of Allergy1687-97911687-9783Hindawi Publishing Corporation49192810.1155/2010/491928491928Review ArticleNeural Pathways in Allergic InflammationMirottiL.1CastroJ.1Costa-PintoF. A.2RussoM.1MoqbelRedwan1Department of ImmunologyInstitute of Biomedical SciencesUniversity of São PauloBrazilusp.br2Department of PathologySchool of Veterinary Medicine and Animal ScienceUniversity of São PauloBrazilusp.br20101912201020100210201030112010081220102010Copyright © 2010 L. Mirotti et al.This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Allergy is on the rise worldwide. Asthma, food allergy, dermatitis, and systemic anaphylaxis are amongst the most common allergic diseases. The association between allergy and altered behavior patterns has long been recognized. The molecular and cellular pathways in the bidirectional interactions of nervous and immune systems are now starting to be elucidated. In this paper, we outline the consequences of allergic diseases, especially food allergy and asthma, on behavior and neural activity and on the neural modulation of allergic responses.

1. Introduction

The prevalence of allergic diseases is continuously increasing. It is estimated that approximately one-third of the general population is affected by allergic diseases. Asthma, food allergy, dermatitis, and systemic anaphylaxis are amongst the most common allergic diseases. The myriad of symptoms observed may involve the airways, the gastrointestinal (GI) tract, the skin, and other systems [1]. The underlying mechanisms involved in the pathophysiology of classic allergic reactions have been well characterized in humans and experimental animal models [24]. Allergic reactions might progress in two distinct phases: an early response, which is characterized by mast cell degranulation and release of inflammatory mediators as a consequence of IgE antibodies cross-linked to their high-affinity receptors (FcεRI) expressed on mast cells membranes, and a late phase response, characterized by a T-helper type 2 (Th2) response, with an increased secretion of cytokines such as IL-4 and IL-13, which stimulate B cells to synthesize IgE; IL-5, necessary for eosinophilic inflammation; IL-9, which stimulates mast cell proliferation [5] (see Figure 1).

Early phase and late phase of allergic hypersensitivity. Upon allergen challenge, sensitized individuals can present two distinct phases: the early phase, which is characterized by mast cell degranulation and release of inflammatory mediators triggered by cross-linking IgE antibodies present on mast cells membranes, and the late phase, that is characterized by the infiltration of Th2 cells that interact with dendritic cells releasing type 2 cytokines responsible for tissue mast cell proliferation and eosinophil recruitment.

There is robust evidence indicating interactions between the immune and nervous systems [6, 7]. There are three types of interactions between the immune system and the central nervous system (CNS); first, the immune system regulates the CNS; second, the CNS drives immunity; third, the CNS acts reciprocally with the immune system. It is well established that these systems, along with the endocrine system, share receptors for cytokines, neurotransmitters, hormones, and neuropeptides. Molecules previously reported as products of a particular system were shown to be more broadly synthesized, such as cytokines being synthesized in the CNS and hormones such as ACTH and TSH being produced by lymphoid cells [814].

This paper will focus on the consequences of allergic diseases, especially food allergy and asthma, on behavior and neural activity and on the bi-directional interaction between immune and nervous systems that culminates with neural modulation of allergic responses.

2. Neural Activity in Allergy

A plethora of epidemiological and clinical data suggests higher incidence of anxiety and increased emotional reactivity in individuals suffering from allergies [1521]. In studies of food allergy, specifically, it has been shown that the prevalence of anxiety or depression is higher in adults with food allergy than in nonhealthy controls with lactose intolerance or in healthy controls [22]. Increased anxiety levels were also associated with food allergy in adolescents [23], and other authors have reported that food allergic children expressed higher levels of anxiety and fear associated with managing their allergy than children with diabetes [24]. Nevertheless, other studies have failed to find association between food allergy and behavioral changes [25, 26]. Asthmatics in crisis also experience changes in emotional status and increased levels of anxiety [27]. Conversely, sadness, stress, and other nervous stimuli can precipitate acute symptoms of asthma [28]. A study using functional magnetic resonance imaging has shown that the activity in the anterior cingulate cortex and insula, in response to asthma-relevant emotional stimuli, is associated with inflammation markers and airway obstruction in asthmatic subjects exposed to antigen [29].

Neuroimmune studies with humans are difficult to be conducted due to the challenge on achieving a precise diagnostic of allergy, the large range of allergic symptoms and severity, artifact of referral bias in population studies, the implication of putatively unrelated psychological factor, psychosomatic aspects of the disease, and ethical issues involved in submitting allergic patients to experimental contact with the allergen [20, 25, 26, 30].

In animal models of allergy, some of the setbacks of behavioral studies can be circumvented, and important findings have been achieved in this area in the last few years. The pioneer work evidencing behavioral changes as consequence of allergic reactions was published by Cara et al. [31]. It was shown that ovalbumin- (OVA-) allergic mice avoid drinking the otherwise preferred saccharin-sweetened solution containing the allergen (OVA) [31]. The protocol used to test the feeding behaviour was based on a two-bottle preference test, in which control or OVA-sensitized animals received water and sweetened OVA-solution in two separate bottles during 24 hours, with no previous conditioning or learning sessions. The immunological aversive phenomenon, known as food aversion, was shown to be abolished by the induction of immunological tolerance [31]. It was also demonstrated that food aversion can be transferred from OVA-allergic to naïve mice by passive transfer (injection of hyperimmune serum) or by adoptive transfer of spleen cells [32]. The immunological aversive behavior was shown to be specific, since peanut- or wheat-sensitized mice, when offered with a mixture of the grains in natura, avoided the ingestion of grains containing the allergen that they were sensitized but not other grains [33].

In view of what is known about food and behavior, including the evolutionary aspects involved with taste recognition [34], a finely constructed system of communication between the digestive system and the brain is entirely plausible. In line with this assumption, it was further demonstrated that OVA-sensitized mice orally challenged with the allergen present increased levels of anxiety, evidenced by shorter time of exploration in the open arms of an elevated plus maze and strong activation of specific brain areas, evidenced by enhanced c-fos expression in the paraventricular nucleus of the hypothalamus (PVN), central nucleus of amygdala (CeA) [35], and nucleus of the solitary tract (NTS) [36] (see Figure 2). Likewise, a different study showed that intestinal anaphylaxis induced important c-fos expression in the PVN, NTS, and lateral parabrachial nucleus (LPB) in mice [37]. PVN and CeA are brain areas related to emotional and affective behavior, and they are amongst the main areas containing corticotropin-releasing hormone- (CRH-) expressing neurons. CRH is a key peptide in co-ordinating the behavioral, neuroendocrine, and autonomic responses to stress [38]; being involved in processes of depression and anxiety [39, 40]. Indeed, clinical and animal studies with different CRH antagonists have evidenced antidepressant effects [4143] and reduction of stress-elicited secretion of cortisol [41]. The activation of CeA [44] and PVN [45, 46] has also been observed in animal models of conditioned taste aversion (CTA), in which animals avoid the consumption of saccharin (conditioned stimulus) after it had been paired with an intraperitoneal injection of lithium chloride (unconditioned, noxious stimulus).

Activation of specific brain areas by c-fos expression. Representative brain coronal sections of nonallergic (nonsensitized) and allergic (OVA-sensitized) mice after (oral or nasal) challenge with OVA. Fos staining in neurons of (a) the paraventricular nucleus of the hypothalamus (PVN), (b) nucleus of the tract solitary (NTS), and (c) central nucleus of the amygdala (CeA). Adapted from Basso et al. 2004 [36] and Costa-Pinto et al. [47].

The cholinergic pathways in allergic lung. During allergic reactions, the inflammatory mediators released in the tissue activate the sensory afferent fibers, which convey information to the CNS. The CNS sends information back to the inflammatory site by increasing ACh release from efferent vagus nerve. The neurotransmission in the parasympathetic ganglia is mediated by acetylcholine (ACh) via nicotinic (nAChR) or type 1 muscarinic (m1AChR) receptors. The stimulus generated induces ACh release in the pos ganglionic nerve fiber endings. Type 2 muscarinic receptors (m2AChRs) are autoinhibitory, and the dysfunction of this receptor, observed in allergic asthma, induces increased release of ACh. Increased ACh results in augmented mucus secretion via m3AchR expressed in the glandular epithelium, increased airway smooth muscle contraction (bronchoconstriction) via m3AchR expressed in muscle cells, and decreased inflammatory mediators production via a7nAChR receptor expressed on immune cells.

In summary, data on food allergy and nervous system demonstrate that, when forced to ingest the allergen (gavage), allergic animals present activation of emotion-related brain areas and increased levels of anxiety [35]. When the option of drinking or not the allergen solution is offered in a two-bottle preference test, allergic animals avoid drinking the allergen solution and prefer drinking water [32, 35].

3. Role of IgE and Mast Cells in Neural Activation

The question that remained to be elucidated is how does the immunological information reach the brain culminating with the neural activation and behavioral change observed? Few studies have focused on this aspect of neuroimmunomodulation; however, some significant findings have been described. The role of IgE in brain activity was determined by the administration of nonanaphylactic anti-IgE antibodies to OVA-sensitized animals. Depletion of IgE prevented c-fos activation in the CNS and food aversion in allergic mice [35]. These results highlight the importance of the early phase of immediate allergic response in the neural/behavioral responses observed. IgE-dependent mast cell activation leads to the secretion of preformed mediators (vasoactive amines, neutral proteases), de novo synthesized proinflammatory lipid mediators, and the synthesis and secretion of other mediators (growth factors, cytokines, and chemokines) [48]. It has been shown that the pre-treatment of OVA-sensitized mice with a mixture containing antagonists of serotonin, via 5-HT2 receptor (methysergide), and histamine, via H1 receptor (mepyramine), inhibited intestinal edema but food aversion was maintained [32]. The pre-treatment with a glucocorticoid (dexamethasone) inhibited both intestinal edema and food aversion [32]. Similar results were observed in rats [49]. This data suggests that the pharmacological effects of histamine or serotonin are not essential to the development of immunological food aversion. The role of dexamethasone may not be directly correlated to immunological aversion since it is known that corticosteroids may have other immunological, anti-inflammatory [50], and psychological effects [51]. The role of other mast cell mediators in the development of food aversive behavior remains to be determined.

Consistent data demonstrates that mast cells are closely apposed to nerve endings [5257], giving anatomical support for the role of mast cells in the interaction between immune system and CNS. Neural pathways most likely to mediate this interaction are the autonomic nervous system, via the vagal nerve and sympathetic nerve fibers to the main sites of the immune system, and afferent nerves that convey visceral sensory information to the CNS [58, 59]. Indeed, mediators such as cytokines released by immune cells have been shown to sensitize afferent neurons [60]. In this vein, neonatal treatment with capsaicin, a neurotoxin derived from chilli pepper (plants from the genus Capsicum) that promotes a selective dysfunction of sensory fibers such as C-fibers [61], completely blocked c-fos expression in the PVN [36] and diminished food aversion in OVA-sensitized mice [62]. The treatment with antagonist of 5-HT3 receptors, expressed in sensory C-fibers [63], diminished the expression of food aversion behavior in sensitized rats [49]. Altogether, these results corroborate the hypothesis that mediators released by mast cell degranulation could stimulate the nerve endings of the C-fibers that, in turn, would transmit the sensory information to the CNS. The presence of IgE receptors (FcεRI) on sensory neurons in mice has been described [64, 65], and this could represent an alternative way of neuron activation, independent on mast cell or basophils. The implications of the direct SNC activation via IgE-antigen interactions should also be considered in the investigations of the role of neural pathways in allergy.

In the theory of taste aversion, the aversive behavior is related to abdominal discomfort [66]. Animals innately seek pleasure and avoid unpleasant sensations. When motivational conflicts between fundamental goals occur, an animal must either endure unpleasant stimulus to attain pleasure or relinquish pleasure to avoid unpleasant situations. We have approached this question by evaluating the behavior of OVA-sensitized mice when facing a conflicting situation in which the aversive stimulus (allergen) was offered associated with an attractive sweet taste (increasing concentrations of sucrose). We found that food aversion was positively correlated with the levels of OVA-specific IgE and inversely correlated with the animal preference for sucrose sweetened solutions. The aversion behavior was abolished by increasing the sucrose concentration (palatability) of the allergen solution [67]. In a broader scenario, this animal model evidenced a complex crosstalk, in which the very sensorial response triggered by a taste preference could be modulated by an immune response. Thus, food aversion is a behavioral adaptive response resultant of a complex and finely controlled process.

In order to determine the effect of allergic asthma on brain activities, parallel studies investigated allergic aversion behavior in an experimental model of allergic lung disease. Using a dark-light box, it was shown that OVA-sensitized mice, differently from control animals, hesitated entering the attracting and supposedly safer, dark chamber in which the allergen had been previously nebulized, preferring the lit (usually aversive) side of the box. Increased activity of the PVN and CeA was also observed in OVA-sensitized mice following a nasal OVA challenge [47].

Using the same experimental model of atopic asthma, it was further demonstrated that the brain and behavior changes observed in OVA-sensitized mice nasally challenged with OVA were (i) IgE dependent, being abrogated by anti-IgE treatment; (ii) mediated by mast cell degranulation, being blocked by the use of sodium cromoglicate (cromolyn, an inhibitor of mast cell degranulation); (iii) not related to airway inflammation, since sensitized C3H/HeJ mice, which did not present pulmonary inflammatory infiltrate, exhibited brain and behavioral changes similar to BALB/c animals [68].

Altogether, the findings described above reinforce the fundamental role of the early phase of allergic response on the brain activation and behavior changes associated with avoidance behavior towards allergen exposure. Also, they highlight the sensory function of the vagus nerve in allergic inflammation.

4. The Serotonergic Pathway in Airway Allergic Inflammation

Atopic asthma is a chronic inflammatory lung disease mediated by Th2 cells, characterized by airway eosinophilia, airway hyperreactivity (AHR), mucus hyper secretion, and elevated levels of IgE. In addition to the roles of classic mediators of allergic inflammation in asthma-like responses, increasing attention is being given to serotonergic receptors in the airways. Plasma levels of serotonin (5-HT) are elevated in symptomatic asthmatic patients [69]. Moreover, 5-HT receptors (5-HTRs) appear to mediate the secretion of cytokines, prostaglandins, and chemokines by alveolar epithelial cells that may aggravate an already complex inflammatory scenario. The mRNA for several 5-HTRs, such as 5-HTR1, 2A, 4, 6, and 7 (seven-transmembrane domain receptors), and 5-HTR3 (ligand-gated ion channel) have been shown in human type-2 alveolar epithelial cells. 5-HT leads to a calcium-mediated, dose-dependent increase in the secretion of IL-6 and IL-8 [70]. Recently, the expression of several 5-HT2 receptor subtypes has been confirmed in mouse alveolar epithelial cells and macrophages by quantitative PCR [71]. In addition, serotonin binding to 5-HT2C receptors in alveolar macrophages leads to increased expression of CCL2 [71]. In a murine model of OVA-induced asthma-like responses, bronchoconstriction can be mediated by 5-HT2 receptor activation in parasympathetic cholinergic neurons, leading in turn to acetylcholine (ACh) release from nerve terminals and smooth muscle contraction [72]. This points to yet another short-loop neuroimmune interaction mediated by 5-HT in allergic asthma. These data altogether strongly suggest a role of 5-HT in the asthmatic inflammatory responses. The increase of ACh and its consequences in airway inflammation will be further discussed in the following sections.

5. The Autonomic Nervous System (ANS) and Immune Responses

The brain and the immune system are hardwired through the autonomic nervous system (ANS), which is composed by the sympathetic nervous system (SNS) and the parasympathetic nervous system (PNS). Description of the innervation of lymphoid organs by the ANS built a solid ground for understanding their implications in health and disease [73].

The role of SNS in modulating inflammatory processes is well described [74, 75]. The SNS has pro- or anti-inflammatory functions depending on factors such as neurotransmitter concentration, receptor affinity, timing of SNS activity in relation to the inflammation course, and others [76]. The SNS richly innervates all lymphoid tissues, including bone marrow, thymus, spleen, mucosal-associated lymphoid tissues, and lymph nodes (for review see [77]). The neurotransmitter released by sympathetic nervous pathways is norepinephrine (NE) although adrenergic neurotransmitters released by the adrenal medulla such as NE and adrenaline also modulate inflammation [75].

The expression of adrenergic receptors in cells of the immune system has been thoroughly reported over the past decades [78]. Noradrenaline, adrenaline, and other ligands estimulate alfa and beta cell surface adrenergic receptors with varied affinities and on several cell types. Beta-2 adrenoceptores are the most commonly found amongst adrenergic receptors in almost all cells of the immune system [79, 80], a noteworthy exception being Th2 clones [81]. Decreased density and signaling via these receptors is usually seen at the peak of T-cell activation, which may be relevant to unleashing these cells to their full potential [82, 83]. Additionally, agonist binding to beta-2 adrenoceptors expressed by B cells, natural killer (NK), and macrophages lead to changes in their activity [8486]. Early evidence of the participation of sympathetic innervation in immunity comes from reports showing a reduction in catecolamine concentration in lymphoid organs following immunization [87]. Several other groups then tackled the issue of NE availability, concentration, and effects during immune responses [74, 8890]. Innervation by the SNS has been fully demonstrated in all lymphoid organs [9194].

Evidence for parasympathetic (cholinergic) innervation of the same sites as those described for SNS is more elusive. Cholinergic innervation is undoubtedly present in the thymus and spleen; however, there is no evidence of parasympathetic innervation of the bone marrow and lymph nodes. Nonetheless, it is now clear that non-noradrenergic neurons enter the parenchyma of lymphoid organs, suggesting several other sources of nervous modulation on immunity [95, 96]. The neurotransmitter released by parasympathetic nervous pathways is ACh.

Contrarily to the well-established role of the SNS in disease, the parasympathetic control of inflammation has only been recently described. The anti-inflammatory role of vagal ACh was shown in animal models of pancreatitis [97], inflammatory bowel disease [98], postoperative ileus [99], lethal endotoxemia [100], and hemorrhagic shock [101]. This phenomenon was named “cholinergic anti-inflammatory pathway” [100].

Besides the ACh released from parasympathetic nerves, it is relevant to mention that there is increasing evidence for extraneuronal ACh signaling, which has been referred to as a “nonneuronal cholinergic system” [102]. In the airways, non-neuronal ACh producer cells include mast cells, monocytes, macrophages, neutrophils, smooth muscle cells, epithelial cells, and lymphocytes [102, 103].

Receptors for various neurotransmitters beyond the sympathetic mediators [79, 104, 105] or parasympathetic [100, 106] are present on immune cells. These neurotransmitters include vasoactive intestinal peptide (VIP), pituitary adenylate cyclase-activating polypeptide [107109], calcitonin gene-related peptide (CGRP), substance P [110, 111], histamine, and serotonin [112, 113]. Likewise, receptors for neuroendocrine mediators, including CRH [114, 115], α-melanocyte-stimulating hormone (α-MSH) [115118], and leptin [115, 119123] are found on lymphoid tissue. These circuits may be also involved in inflammatory response modulation.

6. The Cholinergic Pathway in Airway Allergic Inflammation

Asthma is also associated with increased activity of the parasympathetic nervous system that might underline AHR, one of the hallmarks of asthma. An increase in pulmonary cholinergic nerve activity is associated with asthma, and asthmatic patients are known to be hypersensitive to cholinergic agonists [124]. In fact, the dominant autonomic control of airway smooth muscle in the lungs is provided by the parasympathetic nervous system, and ACh release represents a major bronchoconstrictory pathway. ACh can bind to nicotinic receptors (nAChRs), ligand-gated ion channels comprising 17 different subunits (α1–10, β1–4, γ, δ, ε) [103, 125128], or muscarinic receptors (mAChRs), seven-transmembrane G-protein-coupled receptors that comprise 5 subtypes (M1–M5) [129]. The control of ACh release by the vagus nerve involves autoinhibitory muscarinic M2 receptors expressed on the pos-ganglionic nerve fibers [130].

Interestingly, experimental and clinical data on asthma have evidenced dysfunction of muscarinic M2 autoreceptor, which, in turn, contributed to increased release of ACh from airway parasympathetic nerve endings [131135]. The dysfunction of muscarinic M2 receptor appears to be mediated by eosinophilic major basic protein (MBP), which allosterically blocks muscarinic M2 receptor [130, 136]. The enhanced release of ACh due to M2 dysfunction results in increased airway smooth muscle contraction and mucus secretion via m3AchR present in airway smooth muscle cells and glandular epithelium [137]. Although the increased cholinergic activity of allergic lung contributes to airway flow obstruction, it might have a beneficial effect via the “cholinergic anti-inflammatory pathway.” In this pathway, ACh binds to α7nAChR receptor expressed on immune cells such as macrophages, eosinophils, lymphocytes, and dendritic cells [138]. It has been shown that the activation of this receptor attenuates proinflammatory cytokines release by inhibiting NFκB activation, or via activation of Jak2/STAT3 signaling. The later pathway can negatively regulate NFκB binding to DNA or increase the activity of suppressor of cytokine signaling 3 (SOCS3) that results in inhibition of pro-inflammatory cytokine production (for review see [139]). The involvement of nAChRs other than α7 subtype by the cholinergic anti-inflammatory pathway is suggested by the study of Matsunaga [140]. These authors proposed a role for α4 β2 subunits in the downregulation of IL-6, IL-12, and TNF from murine alveolar macrophages after infection with L. pneumophila [140]. Moreover, α5 nicotinic acetylcholine receptor knockout mice have a more severe experimental colitis than wild-type controls [141]. Finally, it was shown that the vagal inhibition of T-cells proliferation and cytokine release was mediated by an nAChR other than α7 [142].

Notwithstanding the possible participation of other subtypes of nAChRs in asthma, an in vivo model of asthma demonstrated that the activation of α7nAChR reduced the numbers of lymphocytes and eosinophils in the bronchoalveolar lavage (BAL) [143]. Experiments with eosinophils obtained from allergic patients demonstrated that activation of α7nAChR reduced the production of leukotriene C4 and matrix metalloprotease-9 (MMP-9), mediators related to the pathogenesis of asthma [144].

7. Concluding Remarks

In summary, this paper showed that allergic inflammation conveys information to the CNS that, in turn, sends information back to the inflammatory site by releasing neural mediators such as ACh. In asthma, this contributes in smooth muscle contraction (bronchoconstriction) and increased mucus secretion. Similar phenomena occur in the GI tract with increased peristaltism and mucus production. In both cases, these activities that are usually considered as pathologic processes can be viewed as an attempt of the organism to eliminate the irritant stimuli. Therefore, the scenario that emerges from the interaction between immune and nervous systems underscores the robust homeostatic pathways of the brain to allergic inflammation.

OnoS. J.Molecular genetics of allergic diseasesAnnual Review of Immunology2000183473662-s2.0-003412118810.1146/annurev.immunol.18.1.347GouldH. J.SuttonB. J.IgE in allergy and asthma todayNature Reviews Immunology2008832052172-s2.0-4004910167810.1038/nri2273PaulW. E.ZhuJ.How are TH2-type immune responses initiated and amplified?Nature Reviews Immunology20101042252352-s2.0-7795026197510.1038/nri2735de Sousa MucidaD.de Castro KellerA.FernvikE. C.RussoM.Unconventional strategies for the suppression of allergic asthmaCurrent Drug Targets. Inflammation and Allergy2003221871952-s2.0-0642344936MaddoxL.SchwartzD. A.The pathophysiology of asthmaAnnual Review of Medicine2002534774982-s2.0-003618131410.1146/annurev.med.53.082901.103921AderR.CohenN.Behaviorally conditioned immunosuppressionPsychosomatic Medicine19753743333402-s2.0-0016698160Pacheco-LópezG.NiemiM. B.KouW.HärtingM.FandreyJ.SchedlowskiM.Neural substrates for behaviorally conditioned immunosuppression in the ratJournal of Neuroscience2005259233023372-s2.0-1464443436810.1523/JNEUROSCI.4230-04.2005BesedovskyH. O.del ReyA.Immune-neuro-endocrine interactions: facts and hypothesesEndocrine Reviews1996171641022-s2.0-003004389910.1210/er.17.1.64SteinmanL.steinman@stanford.eduElaborate interactions between the immune and nervous systemsNature Immunology20045657558110.1038/ni1078SmithE. M.BlalockJ. E.Human lymphocyte production of corticotropin and endorphin-like substances: association with leukocyte interferonProceedings of the National Academy of Sciences of the United States of America19817812753075342-s2.0-0007981315BlalockJ. E.The immune system as a sensory organJournal of Immunology19841323106710702-s2.0-0021398972KabierschA.del ReyA.HoneggerC. G.BesedovskyH. O.Interleukin-1 induces changes in norepinephrine metabolism in the rat brainBrain Behavior and Immunity1988232672742-s2.0-0024083360BesedovskyH. O.besedovs@mailer.uni-marburg.dedel ReyA.Central and peripheral cytokines mediate immune-brain connectivityNeurochemical Research. In press10.1007/s11064-010-0252-xBoulangerL. M.HuhG. S.ShatzC. J.Neuronal plasticity and cellular immunity: shared molecular mechanismsCurrent Opinion in Neurobiology20011155685782-s2.0-003547739310.1016/S0959-4388(00)00251-8ScottK. M.Von KorffM.OrmelJ.ZhangM. Y.BruffaertsR.AlonsoJ.KesslerR. C.TachimoriH.KaramE.LevinsonD.BrometE. J.Posada-VillaJ.GasquetI.AngermeyerM. C.BorgesG.de GirolamoG.HermanA.HaroJ. M.Mental disorders among adults with asthma: results from the World Mental Health SurveyGeneral Hospital Psychiatry20072921231332-s2.0-3384739195910.1016/j.genhosppsych.2006.12.006HashizumeH.TakigawaM.Anxiety in allergy and atopic dermatitisCurrent Opinion in Allergy and Clinical Immunology2006653353392-s2.0-3374853833810.1097/01.all.0000244793.03239.40NathanR. A.The burden of allergic rhinitisAllergy and Asthma Proceedings2007281392-s2.0-3384760753710.2500/aap.2007.28.2934LavoieK. L.JosephM.BaconaS. L.Psychological distress and occupational asthmaCurrent Opinion in Allergy and Clinical Immunology2009921031092-s2.0-6554916782310.1097/ACI.0b013e32832498c1AtkinsF. M.Food allergy and behavior: definitions, mechanisms and a review of the evidenceNutrition Reviews198644s31041122-s2.0-0022707435CraytonJ. W.Adverse reactions to foods: relevance to psychiatric disordersJournal of Allergy and Clinical Immunology19867812432502-s2.0-0022652123GettisA.Food sensitivities and psychological disturbance: a reviewNutrition and Health1989631351462-s2.0-0024319635AddoloratoG.MarsigliL.CapristoE.CaputoF.Dall'AglioC.BaudanzaP.CammarotaG.GraziosettoR.FoschiF. G.StefaniniG. F.GasbarriniG.Anxiety and depression: a common feature of health care seeking patients with irritable bowel syndrome and food allergyHepato-Gastroenterology19984523155915642-s2.0-7844224393LyonsA. C.FordeE. M. E.Food allergy in young adults: perceptions and psychological effectsJournal of Health Psychology2004944975042-s2.0-304276905510.1177/1359105304044032AveryN. J.KingR. M.KnightS.HourihaneJ. O. B.Assessment of quality of life in children with peanut allergyPediatric Allergy and Immunology20031453783822-s2.0-024249946610.1034/j.1399-3038.2003.00072.xPearsonD. J.RixK. J. B.BentleyS. J.Food allergy: how much in the mind? A clinical and psychiatric study of suspected food hypersensitivityThe Lancet198318336125912612-s2.0-0020623059PevelerR.MayouR.YoungE.StonehamM.Psychiatric aspects of food-related physical symptoms: a community studyJournal of Psychosomatic Research19964121491592-s2.0-003021980410.1016/0022-3999(96)00120-1LawrenceD. A.WrightR. J.Psychologic stress and asthma: neuropeptide involvementEnvironmental Health Perspectives20021105A230A231author reply A2312-s2.0-0036099465LehrerP. M.IsenbergS.HochronS. M.Asthma and emotion: a reviewJournal of Asthma19933015212-s2.0-0027459437RosenkranzM. A.BusseW. W.JohnstoneT.SwensonC. A.CrisafiG. M.JacksonM. M.BoschJ. A.SheridanJ. F.DavidsonR. J.Neural circuitry underlying the interaction between emotion and asthma symptom exacerbationProceedings of the National Academy of Sciences of the United States of America20051023713319133242-s2.0-2494457215310.1073/pnas.0504365102TeufelM.BiedermannT.RappsN.HausteinerC.HenningsenP.EnckP.ZipfelS.Psychological burden of food allergyWorld Journal of Gastroenterology20071325345634652-s2.0-34547396994CaraD. C.CondeA. A.VazN. M.Immunological induction of flavor aversion in miceBrazilian Journal of Medical and Biological Research1994276133113412-s2.0-0028303621CaraD. C.CondeA. A.VazN. M.Immunological induction of flavour aversion in mice. II. Passive/adoptive transfer and pharmacological inhibitionScandinavian Journal of Immunology199745116202-s2.0-0031012331TeixeiraG.Selection of diets by mice immunized to peanuts and cashew nut proteinsDept of Immunology and Biochemistry1995Belo Horizonte, BrazilUFMG, Federal University of MInas GeraisBermúdez-RattoniF.Molecular mechanisms of taste-recognition memoryNature Reviews Neuroscience2004532092172-s2.0-1342268181BassoA. S.Costa PintoF. A.RussoM.Giorgetti BrittoL. R.de Sá-RochaL. C.Palermo NetoJ.Neural correlates of IgE-mediated food allergyJournal of Neuroimmunology20031401-269772-s2.0-003864377710.1016/S0165-5728(03)00166-8BassoA. S.Costa-PintoF. A.Giorgetti BrittoL. R.De Sá-RochaL. C.Palermo-NetoJ.Neural pathways involved in food allergy signaling in the mouse brain: role of capsaicin-sensitive afferentsBrain Research200410091-21811882-s2.0-214270571110.1016/j.brainres.2004.02.062CastexN.FioramontiJ.FargeasM. J.BuenoL.c-fos expression in specific rat brain nuclei after intestinal anaphylaxis: involvement of 5-HT3 receptors and vagal afferent fibersBrain Research19956881-21491602-s2.0-002913489910.1016/0006-8993(95)00526-VHeinrichsS. C.MenzaghiF.PichE. M.BrittonK. T.KoobG. F.The role of CRF in behavioral aspects of stressAnnals of the New York Academy of Sciences1995771921042-s2.0-002954961210.1111/j.1749-6632.1995.tb44673.xArboreliusL.OwensM. J.PlotskyP. M.NemeroffC. B.The role of corticotropin-releasing factor in depression and anxiety disordersJournal of Endocrinology199916011122-s2.0-003289995710.1677/joe.0.1600001MitchellA. J.The role of corticotropin releasing factor in depressive illness: a critical reviewNeuroscience and Biobehavioral Reviews19982256356512-s2.0-003177753810.1016/S0149-7634(97)00059-6HolsboerF.IsingM.Central CRH system in depression and anxiety—evidence from clinical studies with CRH receptor antagonistsEuropean Journal of Pharmacology20085832-33503572-s2.0-4084913005610.1016/j.ejphar.2007.12.032OverstreetD. H.KeeneyA.HoggS.Antidepressant effects of citalopram and CRF receptor antagonist CP-154,526 in a rat model of depressionEuropean Journal of Pharmacology20044922-31952012-s2.0-264251779310.1016/j.ejphar.2004.04.010NielsenD. M.CareyG. J.GoldL. H.Antidepressant-like activity of corticotropin-releasing factor type-1 receptor antagonists in miceEuropean Journal of Pharmacology20044991-21351462-s2.0-1934436793210.1016/j.ejphar.2004.07.091YamamotoT.SakoN.SakaiN.IwafuneA.Gustatory and visceral inputs to the amygdala of the rat: conditioned taste aversion and induction of c-fos-like immunoreactivityNeuroscience Letters199722621271302-s2.0-003096827910.1016/S0304-3940(97)00265-6JahngJ. W.LeeJ. H.LeeS.LeeJ. Y.KimG. T.HouptT. A.KimD. G.Nω-nitro-L-arginine methyl ester attenuates lithium-induced c-Fos, but not conditioned taste aversion, in ratsNeuroscience Research20045044854922-s2.0-964426890610.1016/j.neures.2004.08.016LamprechtR.DudaiY.Differential modulation of brain immediate early genes by intraperitoneal LiClNeuroReport1995712892932-s2.0-0029552617Costa-PintoF. A.BassoA. S.BrittoL. R. G.MalucelliB. E.RussoM.Avoidance behavior and neural correlates of allergen exposure in a murine model of asthmaBrain, Behavior, and Immunity200519152602-s2.0-994424037810.1016/j.bbi.2004.02.005KalesnikoffJ.GalliS. J.New developments in mast cell biologyNature Immunology2008911121512232-s2.0-5454910351410.1038/ni.f.216ZarzanaE. C.BassoA. S.Costa-PintoF. A.Palermo-NetoJ.Pharmacological manipulation of immune-induced food aversion in ratsNeuroImmunoModulation200916119272-s2.0-5744911479410.1159/000179663de BosscherK.HaegemanG.Minireview: latest perspectives on antiinflammatory actions of glucocorticoidsMolecular Endocrinology20092332812912-s2.0-6144922927310.1210/me.2008-0283StuartF. A.SegalT. Y.KeadyS.Adverse psychological effects of corticosteroids in children and adolescentsArchives of Disease in Childhood20059055005062-s2.0-1824440042710.1136/adc.2003.041541BienenstockJ.DenburgJ.ScicchitanoR.SteadR.PerdueM.StaniszA.Role of neuropeptides, nerves and mast cells in intestinal immunity and physiologyMonographs in Allergy1988241341432-s2.0-0023734210BienenstockJ.PerdueM.BlennerhassettM.SteadR.KakutaN.SestiniP.VancheriC.MarshallJ.Inflammatory cells and the epithelium. Mast cell/nerve interactions in the lung in vitro and in vivoAmerican Review of Respiratory Disease19881386S31S342-s2.0-0024264858SteadR. H.DixonM. F.BramwellN. H.RiddellR. H.BienenstockJ.Mast cells are closely apposed to nerves in the human gastrointestinal mucosaGastroenterology19899735755852-s2.0-0024344214WilliamsR. M.BerthoudH. R.SteadR. H.Vagal afferent nerve fibres contact mast cells in rat small intestinal mucosaNeuroimmunomodulation199845-62662702-s2.0-13144251196GreeneR.FowlerJ.MacGlashanD.WeinreichD.IgE-challenged human lung mast cells excite vagal sensory neurons in vitroJournal of Applied Physiology1988645224922532-s2.0-0023912606KiernanJ. A.Degranulation of mast cells in the trachea and bronchi of the rat following stimulation of the vagus nerveInternational Archives of Allergy and Applied Immunology19909143984022-s2.0-0025024203BlalockJ. E.The immune system as the sixth senseJournal of Internal Medicine200525721261382-s2.0-1324429248710.1111/j.1365-2796.2004.01441.xGrundyD.Neuroanatomy of visceral nociception: vagal and splanchnic afferentGut2002511i2i52-s2.0-0036288632MaierS. F.GoehlerL. E.FleshnerM.WatkinsL. R.The role of the vagus nerve in cytokine-to-brain communicationAnnals of the New York Academy of Sciences19988402893002-s2.0-003207742010.1111/j.1749-6632.1998.tb09569.xHolzerP.Capsaicin: cellular targets, mechanisms of action, and selectivity for thin sensory neuronsPharmacological Reviews19914321432012-s2.0-0025871477BassoA. S.de Sá-RochaL. C.Palermo-NetoJ.Immune-induced flavor aversion in mice: modification by neonatal capsaicin treatmentNeuroImmunoModulation20019288942-s2.0-003483835610.1159/000049011LangP. M.Moalem-TaylorG.TraceyD. J.BostockH.GrafeP.Activity-dependent modulation of axonal excitability in unmyelinated peripheral rat nerve fibers by the 5-HT3 serotonin receptorJournal of Neurophysiology2006966296329712-s2.0-3375151199710.1152/jn.00716.2006AndohT.KuraishiY.Expression of Fc epsilon receptor I on primary sensory neurons in miceNeuroReport20041513202920312-s2.0-464432836610.1097/00001756-200409150-00007van der KleijH.CharlesN.KarimiK.MaoYU. K.FosterJ.JanssenL.Chang YangP.KunzeW.RiveraJ.BienenstockJ.Evidence for neuronal expression of functional Fc (ε{lunate} and γ) receptorsJournal of Allergy and Clinical Immunology201012537577602-s2.0-7764927310510.1016/j.jaci.2009.10.054GarciaJ.LasiterP. S.Bermudez-RattoniF.DeemsD. A.A general theory of aversion learningAnnals of the New York Academy of Sciences19854438212-s2.0-0021893335MirottiL.MucidaD.de Sá-RochaL. C.Costa-PintoF. A.RussoM.Food aversion: a critical balance between allergen-specific IgE levels and taste preferenceBrain, Behavior, and Immunity20102433703752-s2.0-7795162231110.1016/j.bbi.2009.12.006Costa-PintoF. A.BassoA. S.RussoM.Role of mast cell degranulation in the neural correlates of the immediate allergic reaction in a murine model of asthmaBrain, Behavior, and Immunity20072167837902-s2.0-3434727017110.1016/j.bbi.2007.01.002LechinF.van der DijsB.OrozcoB.JaraH.RadaI.LechinM. E.LechinA. E.Neuropharmacologic treatment of bronchial asthma with the antidepressant tianeptine: a double-blind, crossover placebo-controlled studyClinical Pharmacology and Therapeutics19986422232322-s2.0-003171122810.1016/S0009-9236(98)90156-4BayerH.MüllerT.MyrtekD.SorichterS.ZiegenhagenM.NorgauerJ.ZisselC.IdzkoM.Serotoninergic receptors on human airway epithelial cellsAmerican Journal of Respiratory Cell and Molecular Biology200736185932-s2.0-3384606596210.1165/rcmb.2006-0151OCEssmanE. J.Serotonin receptors on pulmonary alveolar macrophagesLa Ricerca in Clinica e in Laboratorio198515119242-s2.0-002190197310.1007/BF03029157WeigandL. A.MyersA. C.MeekerS.UndemB. J.Mast cell-cholinergic nerve interaction in mouse airwaysJournal of Physiology200958713335533622-s2.0-6765037004410.1113/jphysiol.2009.173054BellingerL. D.LubahnC.FeltenL. D.Innervation of Lymphoid Organs Association of Nerves with Cells of The Immune System and Their Implications in Diseasein Psychoneuroimmunology20013rdchapter 2New York, NY, USAAcademic PressElenkovI. J.HaskóG.KovácsK. J.ViziE. S.Modulation of lipopolysaccharide-induced tumor necrosis factor-α production by selective α- and β-adrenergic drugs in miceJournal of Neuroimmunology19956121231312-s2.0-002886657210.1016/0165-5728(95)00080-LHaskóG.SzabóC.Regulation of cytokine and chemokine production by transmitters and co-transmitters of the autonomic nervous systemBiochemical Pharmacology1998569107910872-s2.0-003174156610.1016/S0006-2952(98)00153-1StraubR. H.WiestR.StrauchU. G.HärleP.SchölmerichJ.The role of the sympathetic nervous system in intestinal inflammationGut20065511164016492-s2.0-3375034750910.1136/gut.2006.091322BellingerD. L.MillarB. A.PerezS.CarterJ.WoodC.ThyagaRajanS.MolinaroC.LubahnC.LortonD.Sympathetic modulation of immunity: relevance to diseaseCellular Immunology20082521-227562-s2.0-4814909213410.1016/j.cellimm.2007.09.005MaddenK. S.Catecholamines, sympathetic innervation, and immunityBrain, Behavior, and Immunity2003171S5S102-s2.0-003729477410.1016/S0889-1591(02)00059-4SandersV. M.BakerR. A.Ramer-QuinnD. S.KasprowiczD. J.FuchsB. A.StreetN. E.Differential expression of the β-adrenergic receptor by Th1 and Th2 clones implications for cytokine production and B cell helpJournal of Immunology19971589420042102-s2.0-0031135311SandersV. M.MunsonA. E.Beta adrenoceptor mediation of the enhancing effect of norepinephrine on the murine primary antibody response in vitroJournal of Pharmacology and Experimental Therapeutics198423011831922-s2.0-0021214317Ramer-QuinnD. S.BakerR. A.SandersV. M.Activated T helper 1 and T helper 2 cells differentially express the β-2-adrenergic receptor: a mechanism for selective modulation of T helper 1 cell cytokine productionJournal of Immunology199715910485748672-s2.0-0031573079CazauxC. A.Sterin-BordaL.GorelikG.CremaschiG. A.Down-regulation of β-adrenergic receptors induced by mitogen activation of intracellular signaling events in lymphocytesFEBS Letters199536421201242-s2.0-002898812610.1016/0014-5793(95)00366-HDe BlasiA.ParrutiG.SalleseM.Regulation of G protein-coupled receptor kinase subtypes in activated T lymphocytes. Selective increase of β-adrenergic receptor kinase 1 and 2Journal of Clinical Investigation19959512032102-s2.0-0028985273DiamantsteinT.UlmerA.The antagonistic action of cyclic GMP and cyclic AMP on proliferation of B and T lymphocytesImmunology19752811131192-s2.0-0016631162TakamotoT.HoriY.KogaY.ToshimaH.HaraA.YokoyamaM. M.Norepinephrine inhibits human natural killer cell activity in vitroInternational Journal of Neuroscience1991581-21271312-s2.0-0026161827SpenglerR. N.AllenR. M.RemickD. G.StrieterR. M.KunkelS. L.Stimulation of α-adrenergic receptor augments the production of macrophage-derived tumor necrosis factorJournal of Immunology19901455143014342-s2.0-0025070946del ReyA.BesedovskyH. O.SorkinE.Da PradaM.BondiolottiG. P.Sympathetic immunoregulation: difference between high- and low-responder animalsAmerican Journal of Physiology19822421R30R332-s2.0-18344409358KohmA. P.TangY.SandersV. M.JonesS. B.Activation of antigen-specific CD4+ Th2 cells and B cells in vivo increases norepinephrine release in the spleen and bone marrowJournal of Immunology200016527257332-s2.0-0034661985FuchsB. A.CampbellK. S.MunsonA. E.Norepinephrine and serotonin content of the mureine spleen: its relationship to lymphocyte β-adrenergic receptor density and the humoral immune response in vivo and in vitroCellular Immunology198811723393512-s2.0-0024241242MacNeilB. J.JansenA. H.JanzL. J.GreenbergA. H.NanceD. M.Peripheral endotoxin increases splenic sympathetic nerve activity via central prostaglandin synthesisAmerican Journal of Physiology19972732R609R6142-s2.0-0030767095FeltenD. L.LivnatS.FeltenS. Y.Sympathetic innervation of lymph nodes in miceBrain Research Bulletin19841366936992-s2.0-002173330910.1016/0361-9230(84)90230-2SergeevaV. E.Histotopography of catecholamines in the mammalian thymusBulletin of Experimental Biology and Medicine19747744564582-s2.0-0016274102KudohG.HoshiK.MurakamiT.Fluorescence microscopic and enzyme histochemical studies of the innervation of the human spleenArchivum Histologicum Japonicum19794221691802-s2.0-0018627379BesedovskyH. O.Del ReyA.SorkinE.BurriR.HoneggerC. G.SchlumpfM.LichtensteigerW.T lymphocytes affect the development of sympathetic innervation of mouse spleenBrain Behavior and Immunity1987121851932-s2.0-0023354409NanceD. M.SandersV. M.Autonomic innervation and regulation of the immune system (1987–2007)Brain, Behavior, and Immunity20072167367452-s2.0-3434725813410.1016/j.bbi.2007.03.008ShepherdA. J.DowningJ. E. G.MiyanJ. A.Without nerves, immunology remains incomplete—in vivo veritasImmunology200511621451632-s2.0-2544447552510.1111/j.1365-2567.2005.02223.xvan WesterlooD. J.GiebelenI. A.FlorquinS.BrunoM. J.LaRosaG. J.UlloaL.TraceyK. J.van der PollT.The vagus nerve and nicotinic receptors modulate experimental pancreatitis severity in miceGastroenterology20061306182218302-s2.0-3364652217410.1053/j.gastro.2006.02.022GhiaJ. E.BlennerhassettP.Kumar-OndiveeranH.VerduE. F.CollinsS. M.The vagus nerve: a tonic inhibitory influence associated with inflammatory bowel disease in a murine modelGastroenterology20061314112211302-s2.0-3374932116110.1053/j.gastro.2006.08.016TheF. O.BoeckxstaensG. E.SnoekS. A.CashJ. L.BenninkR.LaRosaG. J.van den WijngaardR. M.GreavesD. R.de JongeW. J.Activation of the cholinergic anti-inflammatory pathway ameliorates postoperative ileus in miceGastroenterology20071334121912282-s2.0-3484887340910.1053/j.gastro.2007.07.022BorovikovaL. V.IvanovaS.ZhangM.YangH.BotchkinaG. I.WatkinsL. R.WangH.AbumradN.EatonJ. W.TraceyK. J.Vagus nerve stimulation attenuates the systemic inflammatory response to endotoxinNature200040567854584622-s2.0-003471326610.1038/35013070CaiB.ChenF.JiY.KissL.de JongeW. J.Conejero-GoldbergC.SzaboC.DeitchE. A.UlloaL.Alpha7 cholinergic-agonist prevents systemic inflammation and improves survival during resuscitationJournal of Cellular and Molecular Medicine2009139B377437852-s2.0-7744908345810.1111/j.1582-4934.2008.00550.xWesslerI. K.KirkpatrickC. J.The non-neuronal cholinergic system: an emerging drug target in the airwaysPulmonary Pharmacology and Therapeutics20011464234342-s2.0-003568313610.1006/pupt.2001.0313RackéK.MatthiesenS.The airway cholinergic system: physiology and pharmacologyPulmonary Pharmacology and Therapeutics20041741811982-s2.0-304252545110.1016/j.pupt.2004.03.001WoiciechowskyC.AsadullahK.NestlerD.EberhardtB.PlatzerC.SchöningB.GlöcknerF.LankschW. R.VolkH. D.DöckeW. D.Sympathetic activation triggers systemic interleukin-10 release in immunodepression induced by brain injuryNature Medicine1998478088132-s2.0-003184921410.1038/nm0798-808MillerL. E.GrifkaJ.SchölmerichJ.StraubR. H.Norepinephrine from synovial tyrosine hydroxylase positive cells is a strong indicator of synovial inflammation in rheumatoid arthritisJournal of Rheumatology20022934274352-s2.0-0036196908TraceyK. J.The inflammatory reflexNature200242069178538592-s2.0-003718077810.1038/nature01321VoiceJ. K.GrinningerC.KongY.BangaleY.PaulS.GoetzlE. J.Roles of vasoactive intestinal peptide (VIP) in the expression of different immune phenotypes by wild-type mice and T cell-targeted type II VIP receptor transgenic miceJournal of Immunology200317013083142-s2.0-0037218515GrimmM. C.NewmanR.HassimZ.CuanN.ConnorS. J.LeY.WangJI. M.OppenheimJ. J.LloydA. R.Cutting edge: vasoactive intestinal peptide acts as a potent suppressor of inflammation in vivo by trans-deactivating chemokine receptorsJournal of Immunology200317110499049942-s2.0-0242580114MartinezC.AbadC.DelgadoM.ArranzA.JuarranzM. G.Rodriguez-HencheN.BrabetP.LecetaJ.GomarizR. P.Anti-inflammatory role in septic shock of pituitary adenylate cyclase-activating polypeptide receptorProceedings of the National Academy of Sciences of the United States of America2002992105310582-s2.0-003715416410.1073/pnas.012367999BrainS. D.WilliamsT. J.Substance P regulates the vasodilator activity of calcitonin gene-related peptideNature1988335618573752-s2.0-0023722705SteinhoffM.VergnolleN.YoungS. H.TognettoM.AmadesiS.EnnesH. S.TrevisaniM.HollenbergM. D.WallaceJ. L.CaugheyG. H.MitchellS. E.WilliamsL. M.GeppettiP.MayerE. A.BunnettN. W.Agonists of proteinase-activated receptor 2 induce inflammation by a neurogenic mechanismNature Medicine2000621511582-s2.0-003397123510.1038/72247PedottiR.MitchellD.WedemeyerJ.KarpujM.ChabasD.HattabE. M.TsaiM.GalliS. J.SteinmanL.An unexpected version of horror autotoxicus: anaphylactic shock to a self-peptideNature Immunology2001232162222-s2.0-003528620810.1038/85266JutelM.WatanabeT.KlunkerS.AkdisM.ThometO. A. R.MalolepszyJ.Zak-NejmarkT.KogaR.KobayashiT.BlaserK.AkdisC. A.Histamine regulates T-cell and antibody responses by differential expression of H1 and H2 receptorsNature200141368544204252-s2.0-003595990410.1038/35096564PoliakS.MorF.ConlonP.WongT.LingN.RivierJ.ValeW.SteinmanL.Stress and autoimmunity: the neuropeptides corticotropin-releasing factor and urocortin suppress encephalomyelitis via effects on both the hypothalamic-pituitary-adrenal axis and the immune systemJournal of Immunology199715812575157562-s2.0-0031570394SteinmanL.ConlonP.MakiR.FosterA.The intricate interplay among body weight, stress, and the immune response to friend or foeJournal of Clinical Investigation200311121831852-s2.0-003724403910.1172/JCI200317622GrabbeS.BhardwajR. S.MahnkeK.SimonM. M.SchwarzT.LugerT. A.α-melanocyte-stimulating hormone induces hapten-specific tolerance in miceJournal of Immunology199615624734782-s2.0-0029670721StreileinJ. W.OkamotoS.SanoY.TaylorA. W.Neural control of ocular immune privilegeAnnals of the New York Academy of Sciences20009172973062-s2.0-0033674275FeketeC.LipositsZ.liposits@koki.huHistamine-immunoreactive neurons of the tuberomammillary nucleus are innervated by α-melanocyte stimulating hormone-containing axons. Generation of a new histamine antiserum for ultrastructural studiesBrain Research20039691-2707710.1016/S0006-8993(03)02279-0MatareseG.Di GiacomoA.SannaV.LordG. M.HowardJ. K.Di TuoroA.BloomS. R.LechlerR. I.ZappacostaS.FontanaS.Requirement for leptin in the induction and progression of autoimmune encephalomyelitisJournal of Immunology200116610590959162-s2.0-0035873418SannaV.Di GiacomoA.La CavaA.LechlerR. I.FontanaS.ZappacostaS.MatareseG.Leptin surge precedes onset of autoimmune encephalomyelitis and correlates with development of pathogenic T cell responsesJournal of Clinical Investigation200311122412502-s2.0-003724111310.1172/JCI200316721BaumannH.MorellaK. K.WhiteD. W.DembskiM.BailonP. S.KimH.LaiC. F.TartagliaL. A.The full-length leptin receptor has signaling capabilities of interleukin 6-type cytokine receptorsProceedings of the National Academy of Sciences of the United States of America19969316837483782-s2.0-002977603010.1073/pnas.93.16.8374DemasG. E.Splenic denervation blocks leptin-induced enhancement of humoral immunity in Siberian hamsters (Phodopus sungorus)Neuroendocrinology20027631781842-s2.0-003697344810.1159/000064527RaynerD. V.TrayhurnP.Regulation of leptin production: sympathetic nervous system interactionsJournal of Molecular Medicine20017918202-s2.0-003508890810.1007/s001090100198HaddadEL. B.MakJ. C. W.BelvisiM. G.NishikawaM.RousellJ.BarnesP. J.Muscarinic and β-adrenergic receptor expression in peripheral lung from normal and asthmatic patientsAmerican Journal of Physiology19962706L947L9532-s2.0-0029775155GalziJ. I.ChangeuxJ. P.Neuronal nicotinic receptors: molecular organization and regulationsNeuropharmacology19953465635822-s2.0-002904691310.1016/0028-3908(95)00034-4Conti-TronconiB. M.McLaneK. E.RafteryM. A.GrandoS. A.ProttiM. P.The nicotinic acetylcholine receptor: structure and autoimmune pathologyCritical Reviews in Biochemistry and Molecular Biology1994292691232-s2.0-0028299642LukasR. J.ChangeuxJ. P.Le NovèreN.AlbuquerqueE. X.BalfourD. J. K.BergD. K.BertrandD.ChiappinelliV. A.ClarkeP. B. S.CollinsA. C.DaniJ. A.GradyS. R.KellarK. J.LindstromJ. M.MarksM. J.QuikM.TaylorP. W.WonnacottS.International union of pharmacology. XX. Current status of the nomenclature for nicotinic acetylcholine receptors and their subunitsPharmacological Reviews19995123974012-s2.0-0032970174SgardF.frederic.sgard@sanofi-synthelabo.comCharpantierE.BertrandS.WalkerN.CaputD.GrahamD.BertrandD.BesnardF.A novel human nicotinic receptor subunit, α10, that confers functionality to the α9-subunitMolecular Pharmacology200261115015910.1124/mol.61.1.150EglenR. M.HegdeS. S.WatsonN.Muscarinic receptor subtypes and smooth muscle functionPharmacological Reviews19964845315652-s2.0-0030442725AdamkoD. J.YostB. L.GleichG. J.FryerA. D.JacobyD. B.Ovalbumin sensitization changes the inflammatory response to subsequent parainfluenza infection: eosinophils mediate airway hyperresponsiveness, M2 muscarinic receptor dysfunction, and antiviral effectsJournal of Experimental Medicine199919010146514772-s2.0-003357146810.1084/jem.190.10.1465SchultheisA. H.BassettD. J. P.FryerA. D.Ozone-induced airway hyperresponsiveness and loss of neuronal M2 muscarinic receptor functionJournal of Applied Physiology1994763108810972-s2.0-0028271728LarsenG. L.FameT. M.RenzH.LoaderJ. E.GravesJ.HillM.GelfandE. W.Increased acetylcholine release in tracheas from allergen-exposed IgE- immune miceAmerican Journal of Physiology19942663, part 1L263L2702-s2.0-0028353998FryerA. D.Wills-KarpM.Dysfunction of M2-muscarinic receptors in pulmonary parasympathetic nerves after antigen challengeJournal of Applied Physiology1991716225522612-s2.0-0026357362MinetteP. A. H.LammersJ. W. J.DixonC. M. S.McCuskerM. T.BarnesP. J.A muscarinic agonist inhibits reflex bronchoconstriction in normal but not in asthmatic subjectsJournal of Applied Physiology1989676246124652-s2.0-0024850599AyalaL. E.AhmedT.Is there loss of a protective muscarinic receptor mechanism in asthma?Chest1989966128512912-s2.0-0024331183JacobyD. B.GleichG. J.FryerA. D.Human eosinophil major basic protein is an endogenous allosteric antagonist at the inhibitory muscarinic M2 receptorJournal of Clinical Investigation1993914131413182-s2.0-0027232088RogersD. F.Motor control of airway goblet cells and glandsRespiration Physiology20011251-21291442-s2.0-003512693410.1016/S0034-5687(00)00209-7Rosas-BallinaM.TraceyK. J.Cholinergic control of inflammationJournal of Internal Medicine200926566636792-s2.0-6614910372310.1111/j.1365-2796.2009.02098.xvan WesterlooD. J.The vagal immune reflex: a blessing from aboveWiener Medizinische Wochenschrift20101605-61121172-s2.0-7795253446610.1007/s10354-010-0761-xMatsunagaK.KleinT. W.FriedmanH.YamamotoY.Involvement of nicotinic acetylcholine receptors in suppression of antimicrobial activity and cytokine responses of alveolar macrophages to Legionella pneumophila infection by nicotineJournal of Immunology200116711651865242-s2.0-0035576002Orr-UrtregerA.KedmiM.RosnerS.KarmeliF.RachmilewitzD.Increased severity of experimental colitis in alpha 5 nicotinic acetylcholine receptor subunit-deficient miceNeuroReport20051610112311272-s2.0-2254445629810.1097/00001756-200507130-00018KarimiK.BienenstockJ.WangLU.ForsytheP.The vagus nerve modulates CD4+ T cell activityBrain, Behavior, and Immunity20102423163232-s2.0-7264909737210.1016/j.bbi.2009.10.016BlanchetM. R.Israël-AssayagE.CormierY.Modulation of airway inflammation and resistance in mice by a nicotinic receptor agonistEuropean Respiratory Journal200526121272-s2.0-2174445827710.1183/09031936.05.00116104BlanchetM. R.LangloisA.Israël-AssayagE.BeaulieuM. J.FerlandC.LavioletteM.CormierY.Modulation of eosinophil activation in vitro by a nicotinic receptor agonistJournal of Leukocyte Biology2007815124512512-s2.0-3424787280210.1189/jlb.0906548