Cytokines and autoimmune disease

Abstract

A wide array of cytokines are locally present in autoimmune lesions where they are produced by inflammatory cells or by the target cell of the autoimmune attack. The presence of cytokines at the site of autoaggression reflects ongoing inflammatory and activation processes. These mediators exert proinflammatory effects, contribute to the activation and stimulation of the effector function of T or B lymphocytes, directly participate in target cell destruction, and mediate accompanying local reactions, including fibrotic processes. The release of cytokines into the circulation may explain certain systemic reactions, including fever or changes in the profile of plasma proteins. Many, especially systemic, autoimmune diseases are accompanied by a dysregulation of lymphokine secretion at the level of circulating leukocytes or cells situated outside of the local inflammatory event, thus reflecting regulatory disorders that may either have a genetic or an acquired basis. Decreased production of lymphokines in vitro in response to nonspecific stimuli may be accompanied by an elevated spontaneous release in vivo resulting in an increase of circulating cytokine levels (interleukin 2, tumor necrosis factor-alpha). Secretion of interleukin 1, interleukin 2, and tumor necrosis factors-alpha or -beta, in part, is determined by genetic factors and it is possible that a particular secretor phenotype may predispose to the development of autoimmune lesions. Probably due to their pleiotropic nature, systemic administration of cytokines such as interleukin 1, interleukin 2, tumor necrosis factor, and interferon-gamma may exert either accelerating or suppressive effects on autoimmune diseases. Conversely, agents that block the function of the lymphokine interleukin 2 exert an unequivocal autoimmune disease-inhibiting effect.