Cytokines and autoimmunity

Cytokines have essential roles in immune cell development, immunoregulation and immune effector functions. Cytokines such as interleukin (IL)-2, tumour-necrosis factor (TNF) and the interferons are well known to have immunostimulatory and pro-inflammatory actions. However, the same cytokines also have unexpected, but essential, immunosuppressive actions. IL-2 has essential functions in constraining lymphocyte growth by promoting apoptosis. Regulatory T cells that express the IL-2 receptor γ-chain have also been intensively studied. Deficiency of these cells can result in autoimmunity, but the exact role of IL-2 in the physiology of these cells is unknown. Despite TNF's role as the prototypic cytokine that mediates proinflammatory responses, it is now clear that its in vivo role is complex. Experimental models of disease show that immune-mediated disease, including arthritis, can occur in the absence of TNF. Models of diabetes have shown that TNF can worsen or improve disease, depending on the timing and duration of exposure to this cytokine. Interferons have essential functions in host defence and promote cell-mediated immunity. Type 1 interferons, in particular, have been used to treat autoimmune diseases, including those characterized by T-helper (TH)1-mediated pathology. Type 1 interferons can inhibit secretion of IL-12 and inhibit its action. Type 2 interferon (interferon-γ) and other cytokines upregulate the expression of a class of feedback inhibitors known as suppressors of cytokine signalling (SOCS). Mice deficient in Socs1 have fatal, interferon-dependent, inflammatory disease.