Interleukin-10 prevents experimental allergic encephalomyelitis in rats

• Published in: European journal of immunology Vol. 24; no. 6; p. 1434
• Main Authors: Rott, O, Fleischer, B, Cash, E
• Format: Journal Article
• Language: English
• Published: Germany 01.06.1994
• Subjects: Animals; Cells, Cultured; Encephalomyelitis, Autoimmune, Experimental - immunology; Encephalomyelitis, Autoimmune, Experimental - prevention & control; Flow Cytometry; Histocompatibility Antigens Class II - biosynthesis; Interleukin-10 - therapeutic use; Lymphocyte Activation; Macrophages - drug effects; Myelin Basic Protein - immunology; Rats; Rats, Inbred Lew; T-Lymphocyte Subsets - drug effects; Thymus Gland - cytology; Thymus Gland - drug effects; Tumor Necrosis Factor-alpha - biosynthesis
• ISSN: 0014-2980
• DOI: 10.1002/eji.1830240629

Experimental allergic encephalomyelitis (EAE) is an autoimmune disease mediated by myelin protein-specific CD4+ T lymphocytes of the T(h)1-like phenotype. In rats, the disease is characterized by a monophasic clinical manifestation, followed by a subsequent spontaneous remission and the establishment of life-long resistance to reinduction of disease. Recent data indicate that intracerebral cytokine production, in particular synthesis of interleukin(IL)-10, is selectively up-regulated during the recovery phase of disease. This led us to assess the effects of IL-10 on different rat lymphoid cell functions in vitro and to consider the possibility of an IL-10-mediated treatment to prevent the induction of central nervous system (CNS) autoimmune disease in vivo. Human recombinant IL-10 suppressed interferon-gamma induced major histocompatibility complex class II up-regulation in rat peritoneal macrophages, exhibited pleiotropic effects on thymocytes and totally abrogated tumor necrosis factor production of encephalitogenic T lymphocytes in vitro, without simultaneously affecting proliferative responses of the cells. Upon systemic administration during the initiation phase of disease, IL-10 was effective in markedly suppressing the subsequent induction of EAE in Lewis rats. This suppression of clinical disease coincided with a significant and specific elevation of myelin basic protein-specific autoantibody production, a sustained T cell proliferative response to myelin basic protein and a diminution of CNS infiltrations and thymic involutions in diseased animals. These data implicate IL-10 as a possible candidate for treatment of T(h)1-mediated CNS (auto-) immune diseases.