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

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.