IL-11 inhibits Clostridium difficile toxin A enterotoxicity in rat ileum

被引:37
作者
Castagliuolo, I
Kelly, CP
Qiu, BS
Nikulasson, ST
Lamont, JT
Pothoulakis, C
机构
[1] HARVARD UNIV, DIV GASTROENTEROL, BETH ISRAEL DEACONESS MED CTR, SCH MED, BOSTON, MA 02215 USA
[2] BOSTON UNIV, MED CTR HOSP, SCH MED, DEPT PATHOL, BOSTON, MA 02118 USA
来源
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY | 1997年 / 273卷 / 02期
关键词
interleukin-11; cytokines; diarrhea; colitis; mucosal mast cells; lamina propria macrophages; tumor necrosis factor-alpha;
D O I
10.1152/ajpgi.1997.273.2.G333
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Interleukin-11 (IL-11) is a stromal cell-derived cytokine with several biological activities against hematopoietic cells. Recent results indicated that IL-11 reduced mucosal damage in animal models of colitis. This study aimed to explore the action of recombinant human IL-11 (rhIL-11) on the intestinal effects of Clostridium difficile toxin A, an inflammatory enterotoxin, and cholera toxin, a noninflammatory enterotoxin in rat ileum. We administered rhIL-11 subcutaneously to rats before injection of toxin A into ileal loops and measured fluid secretion, epithelial permeability to mannitol, histopathological damage, and release of rat mast cell protease II (RMCP II) from intestinal mast cells and of tumor necrosis factor-alpha (TNF-alpha) and macrophage inflammatory protein-2 (MIP-2) from lamina propria macrophages. rhIL-11 (50-1,000 mu g/kg) inhibited toxin A but not cholera toxin-mediated secretion and permeability in a dose-dependent fashion and reduced toxin A-induced epithelial cell damage. Rats treated with rhIL-11 also showed reduced RMCP II, TNF-alpha, and MIP-2 release in response to toxin A. Exposure of rat peripheral monocytes in vitro to rhIL-11 (1 mu g/ml) inhibited lipopolysaccharide and toxin A-mediated increases in TNF-alpha mRNA and protein levels. We conclude that rhIL-11 blocks the intestinal effects of C. difficile toxin A, possibly by inhibiting release of inflammatory mediators from mucosal mast cells and intestinal macrophages.
引用
收藏
页码:G333 / G341
页数:9
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