Immunomodulatory effects of interferon beta-1a in multiple sclerosis

Several studies have established a role for interferon beta (IFN beta) as a treatment for relapsing-remitting multiple sclerosis (MS). IFN beta has been reported to decrease the relapse rate, relapse severity, progression of disability and development of new brain lesions. Its mechanisms of action, however, remain unclear. We hypothesize that immunomodulatory effects of IFN beta may underlie its clinical efficacy. We used intracellular cytokine flow cytometry to analyze the effects of IFN beta -1a on expression of the anti-inflammatory cytokine IL-10, and its effects on major co-stimulatory molecules in MS patients. We found that peripheral blood mononuclear cells (PBMC) produced more IL-10 following in vitro or in vivo treatment with IFN beta -1a. The primary cellular sources of IL-10 were monocytes and CD4(-) T lymphocytes. IL-10 production in response to IFN beta -1a was increased in unseparated PBMC compared to purified lymphocyte cultures, indicating that interaction between monocytes and lymphocytes may influence IL-10 production in response to IFN beta -1a. Using flow cytometry, we monitored the ex vivo expression of two major co-stimulatory pairs-B7/CD28 and CD40/CD40L-before and after intramuscular IFN beta -1a treatment of MS patients. IFN beta -1a lowered the expression of B7.1 on circulating B cells and increased B7.2 expression on monocytes. CD40 expression on B cells was down-regulated, but CD40 on monocytes was up-regulated by IFN beta -1a treatment. These data suggest that co-stimulatory molecules are modulated by IFN beta, providing a possible mechanism for its in vivo immune regulatory effects. (C) 2001 Elsevier Science B.V. All rights reserved.