NEUTRALIZATION OF ENDOGENOUS IL-1 RECEPTOR ANTAGONIST EXACERBATES AND PROLONGS INFLAMMATION IN RABBIT IMMUNE COLITIS

被引：147

作者：

FERRETTI, M

CASINIRAGGI, V

PIZARRO, TT

EISENBERG, SP

NAST, CC

COMINELLI, F

机构：

[1] UNIV SO CALIF, LOS ANGELES CTY MED CTR,SCH MED,DEPT MED, DIV GASTROINTESTINAL & LIVER DIS, LOS ANGELES, CA 90033 USA

[2] SYNERGEN INC, BOULDER, CO 80301 USA

[3] CEDARS SINAI MED CTR, DEPT PATHOL, LOS ANGELES, CA 90048 USA

来源：

JOURNAL OF CLINICAL INVESTIGATION | 1994年 / 94卷 / 01期

关键词：

INTERLEUKIN-1; ACUTE INFLAMMATION; MORTALITY; CYTOKINE; INFLAMMATORY BOWEL DISEASE;

D O I：

10.1172/JCI117345

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

Administration of exogenous interleukin-1 receptor antagonist (IL-1ra) is effective in reducing the severity of disease in animal models of acute inflammation. However, the function of endogenous IL-1ra in this process, is not Set known. We investigated the pathophysiological role of IL-1ra in a rabbit model of formalin-immune complex colitis. This model has previously been shown to be IL-1 mediated and a reduction in disease severity is observed with exogenous IL-1ra treatment, Colonic IL-1ra was found to be elevated subsequent to IL-1, and exceeded IL-1 levels 10-fold. Peak levels of IL-1ra preceded both the resolution of colitis and a significant decrease in IL-1 production. Administration of specific neutralizing antibodies against rabbit IL-1ra increased mortality and prolonged intestinal inflammatory responses. A significant increase in IL-1 alpha colonic tissue levels was also measured as a result of exogenous anti-IL-1ra treatment. These studies are the first demonstration that endogenous IL-1ra may play an important role in regulating the host's inflammatory response by counteracting the deleterious and possibly lethal effects of IL-1 produced during acute inflammation.

引用

页码：449 / 453

页数：5

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