Interferon beta induces interleukin-10 expression: relevance to multiple sclerosis

Abstract

Interferon-beta decreases the relapse rate, relapse severity, progression of neurological disability, and development of new brain lesions observed with brain magnetic resonance imaging in relapsing-remitting multiple sclerosis patients. The mechanism of action of this effect is presently unknown. This study was based on the hypothesis that immunoregulatory effects of interferon-beta may underlie its demonstrated clinical efficacy. The objective of the study was to determine the effect of interferon-beta-1a on the expression of interleukin-10, a cytokine that strongly inhibits cell-mediated immune responses. Interferon-beta-1a induced accumulation of interleukin-10 messenger RNA and protein secretion by cultured peripheral blood mononuclear cells. The observed in vitro effects were similar for healthy control subjects and multiple sclerosis patients. Intramuscular injections of interferon-beta-1a increased serum levels of interleukin-10 at 12 and 24 hours following the injection. Greater increases were induced with 12 x 10(6)-IU than 6 x 10(6)-IU injections. The effect of interferon-beta-1a was relatively specific for interleukin-10, as treatment with interferon-beta-1a did not result in accumulation of transforming growth factor-beta messenger RNA. Upregulation of interleukin-10 represents a possible mechanism of action of interferon-beta's therapeutic effect in relapsing-remitting multiple sclerosis, and has implications for therapy of other autoimmune diseases.