Induction of IL-1 receptor antagonist by interferon beta: implication for the treatment of multiple sclerosis.
IFNbeta 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 IFNbeta administration in MS patients. We now report that IFNbeta 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-1beta, IFNgamma, IL-4, dexamethasone). This prolonged and quantitatively elevated induction of IL-1ra may contribute to the anti-inflammatory effect of IFNbeta and partially account for the reduction of exacerbation rate shown in most IFNbeta-treated MS patients.
Sciacca
F L
FL
Neuroimmunology Unit, San Raffaele Scientific Institute, Milan, Italy.
Canal
N
N
Grimaldi
L M
LM
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000906:Antibodies / Q000494:pharmacology; D015152:Blotting, Northern; D015870:Gene Expression / Q000187:drug effects / Q000276:immunology; D006801:Humans; D016899:Interferon-beta / Q000276:immunology / Q000494:pharmacology*; D053590:Interleukin 1 Receptor Antagonist Protein; D007948:Leukemia, Monocytic, Acute; D009000:Monocytes / Q000166:cytology / Q000276:immunology; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000276:immunology*; D012333:RNA, Messenger / Q000378:metabolism; D012795:Sialoglycoproteins / Q000235:genetics* / Q000276:immunology*; D020298:U937 Cells
D000276:Adjuvants, Immunologic; D000906:Antibodies; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D012333:RNA, Messenger; D012795:Sialoglycoproteins; D016899:Interferon-beta