Interleukin-10 prevents experimental allergic encephalomyelitis in rats.
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.
Rott
O
O
INSERM U.283, Hopital Cochin, Paris, France.
Fleischer
B
B
Cash
E
E
D000818:Animals; D002478:Cells, Cultured; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000517:prevention & control*; D005434:Flow Cytometry; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis; D016753:Interleukin-10 / Q000627:therapeutic use*; D008213:Lymphocyte Activation; D008264:Macrophages / Q000187:drug effects; D004676:Myelin Basic Protein / Q000276:immunology; D051381:Rats; D011917:Rats, Inbred Lew; D016176:T-Lymphocyte Subsets / Q000187:drug effects; D013950:Thymus Gland / Q000166:cytology / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D000949:Histocompatibility Antigens Class II; D004676:Myelin Basic Protein; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10