Hedegaard Chris J, Krakauer Martin, Bendtzen Klaus, Sørensen Per Soelberg, Sellebjerg Finn, Nielsen Claus H
Institute for Inflammation Research, University Hospital of Copenhagen, Rigshospitalet, Copenhagen, Denmark.
Clin Immunol. 2008 Oct;129(1):80-9. doi: 10.1016/j.clim.2008.06.007. Epub 2008 Jul 23.
Interferon (IFN)-beta therapy has well-established clinical benefits in multiple sclerosis (MS), but the underlying modulation of cytokine responses to myelin self-antigens remains poorly understood. We analysed the CD4+ T cell proliferation and cytokine responses elicited by myelin basic protein (MBP) and a foreign recall antigen, tetanus toxoid (TT), in mononuclear cell cultures from fourteen MS patients undergoing IFN-beta therapy. The MBP-elicited IFN-gamma-, TNF-alpha- and IL-10 production decreased during therapy (p<0.007-0.03), while the IL-6 production increased (p<0.03). No significant change was observed in the MBP-induced CD4+ T cell proliferation, or in the production of IL-4, IL-5 and brain-derived neurotrophic factor. In comparison, IFN-beta therapy reduced IFN-gamma and IL-4 responses to TT (p<0.003 and p<0.04). Thus, IFN-beta inhibits IFN-gamma production in general, presumably alleviating the detrimental influence of IFN-gamma in MS. However, the increase in proinflammatory IL-6 and the decrease in anti-inflammatory IL-10 responses suggest that IFN-beta has more diverse effects than previously assumed.
干扰素（IFN）-β疗法在多发性硬化症（MS）中具有公认的临床益处，但对髓鞘自身抗原的细胞因子反应的潜在调节仍知之甚少。我们分析了14例接受IFN-β治疗的MS患者单核细胞培养物中，髓鞘碱性蛋白（MBP）和外来回忆抗原破伤风类毒素（TT）引发的CD4+T细胞增殖和细胞因子反应。治疗期间，MBP引发的IFN-γ、TNF-α和IL-10产生减少（p<0.007-0.03），而IL-6产生增加（p<0.03）。MBP诱导的CD4+T细胞增殖以及IL-4、IL-5和脑源性神经营养因子的产生未观察到显著变化。相比之下，IFN-β治疗降低了对TT的IFN-γ和IL-4反应（p<0.003和p<0.04）。因此，IFN-β总体上抑制IFN-γ的产生，可能减轻了IFN-γ在MS中的有害影响。然而，促炎IL-6的增加和抗炎IL-10反应的减少表明，IFN-β的作用比以前认为的更多样化。
