Interferon-β therapy for multiple sclerosis induces reciprocal changes in interleukin-12 and Interleukin-10 production

Adriana A. Byrnes, Justin C. McArthur, Christopher L. Karp

Research output: Contribution to journalArticle

Abstract

Interleukin-12 is critical to the pathogenesis of experimental autoimmune encephalomyelitis in multiple species. Interleukin-10, a dominant endogenous inhibitor of interleukin-12, is largely protective in these experimental surrogates for multiple sclerosis. Such data have suggested that an interleukin-12/interleukin-10 immunoregulatory circuit is a key determinant of disease expression in experimental autoimmune encephalomyelitis. For multiple sclerosis itself, compatible cytokine data have been reported. The mechanisms underlying the beneficial effects of interferon-β in multiple sclerosis remain unclear, hampering the search for more effective therapies. Of note, interferon-β has reciprocal effects on these cytokines in vitro, suppressing interleukin-12 and augmenting interleukin-10 production. To examine the effects of interferon-β on the interleukin-12/interleukin-10 axis in multiple sclerosis, we characterized the production of these cytokines by peripheral blood mononuclear cells from patients beginning therapy with interferon-β. Before therapy, multiple sclerosis patients exhibited increased stimulatable interleukin-12 production compared with controls. Interferon-β therapy leads to inhibition of interleukin-12 and augmentation of interleukin-10 production, significantly elevating the ratio of secreted interleukin-10 to interleukin-12. These effects, observed equally in patients with relapsing-remitting and progressive disease, indicate that interferon-β affects the interleukin-12/interleukin-10 axis in ways thought to be beneficial to multiple sclerosis patients. More specific therapeutic targeting of these pathways may be warranted.

Original languageEnglish (US)
Pages (from-to)165-174
Number of pages10
JournalAnnals of neurology
Volume51
Issue number2
DOIs
StatePublished - Feb 11 2002

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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