title: Interferon-beta therapy for multiple sclerosis induces reciprocal changes in interleukin-12 and interleukin-10 production.
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.
authors.affiliation: Department of Medicine, Johns Hopkins University Schools of Medicine and Public Health, Baltimore, MD, USA.
authors.forename: Adriana A
authors.initials: AA
authors.lastname: Byrnes
authors.forename: Justin C
authors.initials: JC
authors.lastname: McArthur
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Karp
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000328:Adult; D000368:Aged; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D016899:Interferon-beta / Q000494:pharmacology*; D016753:Interleukin-10 / Q000096:biosynthesis* / Q000378:metabolism; D018664:Interleukin-12 / Q000096:biosynthesis* / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D020528:Multiple Sclerosis, Chronic Progressive / Q000188:drug therapy / Q000276:immunology; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy* / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D016753:Interleukin-10; D018664:Interleukin-12; D016899:Interferon-beta