Association of IL10 Production with Autoimmune Diseases

A number of studies of both mouse and human models of autoimmune diseases have documented altered IL-10 serum levels, suggesting a direct link between IL-10 levels and disease.1'2 Evidence from mouse models suggest that IL-10 production may play a protective role in organ-specific autoimmune disease and alter the balance between pathogenic Th1 cells and protective anti-inflammatory Th2 cells.2 However, while some studies show that administration of IL-10 could result in improvement of the disease phenotype, other studies have shown that IL-10-deficient mice fail to develop an autoimmune syndrome, and the expression of an IL-10 transgene resulted in earlier disease onset or exacerbated disease rather than in protection.2

High serum levels of IL-10 have been documented in human autoimmune diseases. In systemic lupus erythematosus (SLE) patients, high IL-10 levels have been shown to correlate with disease activity,9,10 and studies indicate that cultured PBMC from lupus patients spontaneously produce high levels of IL-10.1 Production of high levels of IL-10 has also been demonstrated in synovial T-lymphocytes of rheumatoid arthritis patients, in the serum of systemic sclerosis, Kawasaki disease, and ALPS patients, as well as in the cultured cells of polymyositis and dermatomyositis patients.2 High IL-10 levels have been found in the blister fluid of pemphigus vulgaris and bullous pemphigoid patients and in the mucosal T cells in ulcerative coli-tis.2,11-16 Increased expression of IL-10 mRNA by PBMCs and/or various other tissues was associated with Sjogren's syndrome, Grave's disease, myasthenia gravis, psoriasis and autoimmune lymphoproliferative syndrome (ALPS).1,2,8,16,17 Taken together, these studies indicate that dysregulated expression of IL-10 plays a significant role in autoimmune diseases. While the disease association with IL-10 levels is clear, the degree to which IL-10 production precedes disease onset, as opposed to resulting from disease activity, is less clear. In addition, while autoimmune disease progression may play a role in altering the levels of IL-10 and other cytokines, evidence from family studies suggest that, to a large extent, heritable genetic differences determine IL-10 production and thus contribute to autoimmune disease phenotype.18,19 The association of high levels of IL-10 mRNA and protein with early stages of Grave's disease and Hashimoto's thyroiditis also suggests a role for IL-10 in the early stages of some diseases.8

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