Kojouharoff G, Hans W, Obermeier F, Männel D N, Andus T, Schölmerich J, Gross V, Falk W
Department of Internal Medicine I, University of Regensburg, Germany.
Clin Exp Immunol. 1997 Feb;107(2):353-8. doi: 10.1111/j.1365-2249.1997.291-ce1184.x.
The cytokines TNF and IL-1 have been implicated as mediators of the inflammatory processes in patients with inflammatory bowel disease (IBD). To investigate the role of these cytokines in mucosal inflammation we used anti-cytokine strategies in a mouse model of acute and chronic colitis. Mice which received 5% dextran sulphate sodium (DSS) in their drinking water showed signs of acute colitis on day 4, with severe weight loss and bloody diarrhoea. Chronic colitis was established after four cycles of feeding 5% DSS for 7 days and water for 10 days, with the mice showing diarrhoea but no weight loss. In acute colitis, treatment with anti-IL-1 reagents, anti-TNF MoAb, or dexamethasone (DEX) led to aggravation. By contrast, in chronic colitis, treatment of mice with several IL-1 activity-inhibiting reagents failed to show significant effects, whereas anti-TNF MoAb or DEX significantly reduced the colitis. We conclude that in acute colitis IL-1 and TNF are beneficial, whereas in chronic colitis, TNF but not IL-1 seems to play a major role in perpetuation of chronic inflammation.
细胞因子肿瘤坏死因子（TNF）和白细胞介素-1（IL-1）被认为是炎症性肠病（IBD）患者炎症过程的介质。为了研究这些细胞因子在黏膜炎症中的作用，我们在急性和慢性结肠炎小鼠模型中采用了抗细胞因子策略。饮用含5%硫酸葡聚糖钠（DSS）水的小鼠在第4天出现急性结肠炎迹象，伴有严重体重减轻和血性腹泻。在经过四个饲喂周期（5% DSS 7天、水10天）后建立慢性结肠炎，小鼠出现腹泻但体重未减轻。在急性结肠炎中，用抗IL-1试剂、抗TNF单克隆抗体或地塞米松（DEX）治疗会导致病情加重。相比之下，在慢性结肠炎中，用几种抑制IL-1活性的试剂治疗小鼠未显示出显著效果，而抗TNF单克隆抗体或DEX可显著减轻结肠炎。我们得出结论，在急性结肠炎中IL-1和TNF是有益的，而在慢性结肠炎中，TNF而非IL-1似乎在慢性炎症的持续存在中起主要作用。
