Constantinescu C S, Wysocka M, Hilliard B, Ventura E S, Lavi E, Trinchieri G, Rostami A
Department of Neurology, University of Pennsylvania, Philadelphia 19104, USA.
J Immunol. 1998 Nov 1;161(9):5097-104.
Immunization of (PL/J x SJL/J)F1 mice with myelin basic protein (MBP) induces relapsing experimental autoimmune encephalomyelitis (EAE). Relapses occur 7 to 10 days after recovery from the initial paralysis. Staphylococcal enterotoxins (SE) A or B, administered after recovery from the initial paralysis, induce immediate relapses. IL-12 is involved in the induction of EAE. Here, we show that SEA and SEB induce IL-12 in splenocytes from (PL/J x SJL/J)F1 mice in vitro and increase the level of IL-12 in the sera of mice treated with these superantigens. IL-12 administration mimics SE in inducing spontaneous relapses and in enhancing the severity and frequency of spontaneous relapses. IL-12 neutralization blocks SE-induced and subsequent relapses of EAE, and, when instituted after recovery from the initial attack, prevents spontaneous relapse. This is the first report of prevention of relapses of EAE with anti-IL-12 Ab, an approach which may prove useful in the prevention of exacerbations in multiple sclerosis.
用髓鞘碱性蛋白（MBP）免疫（PL/J×SJL/J）F1小鼠可诱发复发性实验性自身免疫性脑脊髓炎（EAE）。复发发生在初次瘫痪恢复后的7至10天。在初次瘫痪恢复后给予葡萄球菌肠毒素（SE）A或B可诱发立即复发。IL-12参与EAE的诱导。在此，我们表明SEA和SEB在体外可诱导（PL/J×SJL/J）F1小鼠脾细胞产生IL-12，并增加用这些超抗原处理的小鼠血清中IL-12的水平。给予IL-12在诱导自发复发以及增强自发复发的严重程度和频率方面模拟了SE的作用。中和IL-12可阻断SE诱导的EAE复发及随后的复发，并且在初次发作恢复后进行时可防止自发复发。这是关于用抗IL-12抗体预防EAE复发的首次报道，这种方法可能被证明对预防多发性硬化症的病情加重有用。
