To identify whether cytokines, cytokine-related factors, and
chemokines are up-regulated prior to the development of
rheumatoid arthritis (RA).   A nested case–control study was
performed in 86 individuals who had donated blood samples before
experiencing any symptoms of disease (pre-patients) and 256
matched control subjects (1:3 ratio). In 69 of the pre-patients,
blood samples were also obtained at the time of the diagnosis of
RA. The plasma levels of 30 cytokines, related factors, and
chemokines were measured using a multiplex system.   The levels
of several of the cytokines, cytokine receptors, and chemokines
were significantly increased in individuals before disease onset
compared with the levels in control subjects; i.e., those
representing signs of general immune activation (interleukin-1β
[IL-1β], IL-2, IL-6, IL-1 receptor antagonist, and tumor
necrosis factor), activation of Th1 cells (interferon-γ, IL-12),
Th2 cells (IL-4, eotaxin), Treg cells (IL-10), bone
marrow–derived factors (IL-7, granulocyte–