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

Ann Neurol. 2002 Feb;51(2):165-74. doi: 10.1002/ana.10084.

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-beta in multiple sclerosis remain unclear, hampering the search for more effective therapies. Of note, interferon-beta has reciprocal effects on these cytokines in vitro, suppressing interleukin-12 and augmenting interleukin-10 production. To examine the effects of interferon-beta 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-beta. Before therapy, multiple sclerosis patients exhibited increased stimulatable interleukin-12 production compared with controls. Interferon-beta 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-beta 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adjuvants, Immunologic / pharmacology*
  • Adult
  • Aged
  • Female
  • Humans
  • In Vitro Techniques
  • Interferon-beta / pharmacology*
  • Interleukin-10 / biosynthesis*
  • Interleukin-10 / metabolism
  • Interleukin-12 / biosynthesis*
  • Interleukin-12 / metabolism
  • Leukocytes, Mononuclear / drug effects
  • Leukocytes, Mononuclear / immunology
  • Leukocytes, Mononuclear / metabolism
  • Male
  • Middle Aged
  • Multiple Sclerosis, Chronic Progressive / drug therapy
  • Multiple Sclerosis, Chronic Progressive / immunology
  • Multiple Sclerosis, Relapsing-Remitting / drug therapy*
  • Multiple Sclerosis, Relapsing-Remitting / immunology

Substances

  • Adjuvants, Immunologic
  • Interleukin-10
  • Interleukin-12
  • Interferon-beta