Immunostimulant Drugs for Autoimmune Disease: Safer Alternatives to Steroids and Other Immunosuppressive Treatment

Most treatments for autoimmune diseases (such as multiple sclerosis, rheumatoid arthritis, psoriasis and lupus/SLE) are immunosuppressants. These drugs work by decreasing immune function. Often they do help, but can have dangerous side effects.

Immunosuppressant drugs include e.g. prednisone, dexamethasone and other steroids, mycophenolate mofetil and the new biological drugs such as infliximab (Remicade), efalizumab (Raptiva) and natalizumab (Tysabri). Refractory autoimmune diseases are sometimes treated with chemotherapeutic drugs such as mitoxantrone, cyclophosphamide or methotrexate.

The reason immunosuppressants are used is because autoimmune disease was thought to be caused by overactivity of the immune system, but this theory is increasingly being questioned. Many doctors and researchers now think autoimmunity is in fact a type of immune deficiency.

Problems with Immunosuppressants

Steroids like prednisone are notorious for their adverse effects, such as weight gain, mood swings, diabetes, bone and muscle loss, cataracts and joint damage. Chemotherapy is usually used in smaller doses than in cancer, but they can still cause very unpleasant side effects, including the dreaded hair loss.

The problem with immunosuppressant drugs in general is that the immune system usually needs to be suppressed quite a bit in order to reduce autoimmune disease activity. The immune system is very important for protecting the body from viral, bacterial and fungal infections and cancer, but immunosuppressants weaken this protection and thus raise the risk of many serious conditions

The newer biological drugs are much more specific in their action (suppressing the immune system more selectively) than e.g. steroids and initially they were thought to be safer, but they are not without problems. E.g. Raptiva and Tysabri have been connected with PML, a deadly brain infection caused by a normally harmless virus, which resulted in withdrawal of Raptiva.

Also, if autoimmune disease is caused by a poorly working immune system instead of an overactive one, this conventional approach is not only counter-intuitive, but also potentially harmful.

Treating Autoimmune Diseases with Immunostimulants

Traditionally immunostimulants have been believed to worsen autoimmune disease, to the point that some immunostimulants have originally been classified as immunosuppressants because they were found to improve autoimmune disease. But in practice it does not seem to work like that.

If the theory that autoimmune disease is in fact a type of an immune deficiency – or that there are components of immune deficiency, as the immune system is highly complex and not necessarily easy to define as “overactive” or “underactive” – is correct, immunostimulants would be the rational choice of treatment.

Immunostimulants are not completely without risks or side effects, but some of them can get quite close. They do not increase the risk of infections and cancer – and may even reduce the risk.

The most conventionally accepted immunostimulant therapy for autoimmune diseases is intravenous immunoglobulin (also known as IVIG and gammaglobulin), a blood product that contains antibodies from thousands of donors. It has been used in e.g. multiple sclerosis and myasthenia gravis, but because of high expenses it is usually reserved for refractory and life-threatening cases.

Low dose naltrexone (LDN) has been used in the treatment of multiple sclerosis and other autoimmune diseases since the 1980s. Low dose naltrexone works by boosting the levels of endogenous opioid peptides (which are deficient in autoimmune disease) that help to regulate the immune system with some immunostimulant effects.

LDN was recently trialed in primary progressive multiple sclerosis (PPMS) and excellent results were achieved in a study for Crohn’s disease which results was published on It is currently in trials for e.g. juvenile Crohn’s disease, autism and fibromyalgia. LDN is very inexpensive and no major side effects or illness exacerbations have ever been reported. It is also taken orally.

Another oral immunostimulant drug inosine pranobex/isoprinosine (Imunovir) has been the subject of a few studies that suggested it may be helpful in rheumatic diseases (lupus/SLE, rheumatoid arthritis and systemic sclerosis), multiple sclerosis and alopecia areata. The related over-the-counter supplement inosine is currently in clinical trials for multiple sclerosis.

There are some new immunostimulant drugs in clinical trials for autoimmune diseases, but sadly, most of the medications being developed for autoimmune diseases are still immunosuppressants.