Interleukin‐10 prevents experimental allergic encephalomyelitis in rats

Abstract

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.

Cytokine expression by inflammatory cells obtained from the spinal cords of Lewis rats with experimental autoimmune encephalomyelitis induced by inoculation with myelin basic protein and adjuvants

“…Previous studies are unclear about the role of IL-10 in recovery from EAE. One study in the rat (Rott et al, 1994) found that exogenous IL-10 reduced the severity of EAE, whereas another study, in mice, found the opposite (Cannella et al, 1996). Thus, we found increased expression of all cytokines, relative to the expression of -actin, during late clinical recovery, near the time that spontaneous relapses of EAE can occur.…”

Different Therapeutic Outcomes in Experimental Allergic Encephalomyelitis Dependant Upon the Mode of Delivery of IL-10: A Comparison of the Effects of Protein, Adenoviral or Retroviral IL-10 Delivery into the Central Nervous System

“…IL-10 has been shown to have a half-life of around 2 h in vivo (21) and a previous study administering large quantities of IL-10 frequently, showed that EAE could be prevented when administered systemically during the priming phase of EAE (6). However, should IL-10 be of therapeutic benefit, then it should be administered once the autoaggressive response has already been generated.…”

Murine IL-10 Gene Transfer Inhibits Established Collagen-Induced Arthritis and Reduces Adenovirus-Mediated Inflammatory Responses in Mouse Liver

“…I nterleukin-10 is an immunoregulatory cytokine that has been shown to possess potential therapeutic value for organ-specific autoimmune diseases, as it reduces symptoms of experimental diabetes (1,2), autoimmune encephalomyelitis (3,4), inflammatory bowel disease (5), and autoimmune arthritis (6 -9).…”