Induction of IL-1 receptor antagonist by interferon beta: Implication for the treatment of multiple sclerosis

IFNβ has been the first drug approved for the treatment of multiple sclerosis patients, but we still lack a full understanding of the mechanisms underlying its clinical effects and the great variability of its therapeutic efficacy among different patients. Serum levels of the anti-inflammatory cytokine IL-1 receptor antagonist increase after IFNβ administration in MS patients. We now report that IFNβ induced IL-1ra mRNA and mature protein in three myelomonocytic cell lines. The induction of IL-1ra was already visible after 2 h of stimulation and persisted at least for 24 h. The amounts of induced IL-1ra were equal or higher than those obtained using other IL-1ra stimuli (LPS, IL-1β, IFNγ, IL-4, dexamethasone). This prolonged and quantitatively elevated induction of IL-1ra may contribute to the anti-inflammatory effect of IFNβ and partially account for the reduction of exacerbation rate shown in most IFNβ-treated MS patients.