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Glatiramer acetate increases IL-1 receptor antagonist but decreases T cell-induced IL-1beta in human monocytes and multiple sclerosis

Weber, Martin S.
Zamvil, Scott S.
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Published in Proceedings of the National Academy of Sciences. 2009, vol. 106, no. 11, p. 4355-4359
Abstract Mechanisms of action as well as cellular targets of glatiramer acetate (GA) in multiple sclerosis (MS) are still not entirely understood. IL-1beta is present in CNS-infiltrating macrophages and microglial cells and is an important mediator of inflammation in experimental autoimmune encephalitis (EAE), the MS animal model. A natural inhibitor of IL-1beta, the secreted form of IL-1 receptor antagonist (sIL-1Ra) improves EAE disease course. In this study we examined the effects of GA on the IL-1 system. In vivo, GA treatment enhanced sIL-1Ra blood levels in both EAE mice and patients with MS, whereas IL-1beta levels remained undetectable. In vitro, GA per se induced the transcription and production of sIL-1Ra in isolated human monocytes. Furthermore, in T cell contact-activated monocytes, a mechanism relevant to chronic inflammation, GA strongly diminished the expression of IL-1beta and enhanced that of sIL-1Ra. This contrasts with the effect of GA in monocytes activated upon acute inflammatory conditions. Indeed, in LPS-activated monocytes, IL-1beta and sIL-1Ra production were increased in the presence of GA. These results demonstrate that, in chronic inflammatory conditions, GA enhances circulating sIL-1Ra levels and directly affects monocytes by triggering a bias toward a less inflammatory profile, increasing sIL-1Ra while diminishing IL-1beta production. This study sheds light on a mechanism that is likely to participate in the therapeutic effects of GA in MS.
Keywords AnimalsEncephalomyelitis, Autoimmune, Experimental/drug therapyHumansImmunosuppressive Agents/pharmacologyInflammation/drug therapyInterleukin 1 Receptor Antagonist Protein/blood/*drug effectsInterleukin-1beta/*drug effectsMiceMonocytes/*immunologyMultiple Sclerosis/*drug therapy/immunologyPeptides/*pharmacologyTranscription, Genetic
PMID: 19255448
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Research group Inflammation et allergie (874)
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BURGER, Danielle et al. Glatiramer acetate increases IL-1 receptor antagonist but decreases T cell-induced IL-1beta in human monocytes and multiple sclerosis. In: Proceedings of the National Academy of Sciences, 2009, vol. 106, n° 11, p. 4355-4359. doi: 10.1073/pnas.0812183106 https://archive-ouverte.unige.ch/unige:19718

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Deposited on : 2012-04-23

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