IL-11 INHIBITS CLOSTRIDIUM-DIFFICILE TOXIN-A ENTEROTOXICITY IN RAT ILEUM

Interleukin-11 (IL-11) is a stromal cell-derived cytokine with several biological activities against hematopoietic cells. Recent results ind icated that IL-11 reduced mucosal damage in animal models of colitis. This study aimed to explore the action of recombinant human IL-11 (rhI L-11) on the intestinal effects of Clostridium difficile toxin A, an i nflammatory enterotoxin, and cholera toxin, a noninflammatory enteroto xin in rat ileum. We administered rhIL-11 subcutaneously to rats befor e injection of toxin A into ileal loops and measured fluid secretion, epithelial permeability to mannitol, histopathological damage, and rel ease of rat mast cell protease II (RMCP II) from intestinal mast cells and of tumor necrosis factor-alpha (TNF-alpha) and macrophage inflamm atory protein-2 (MIP-2) from lamina propria macrophages. rhIL-11 (50-1 ,000 mu g/kg) inhibited toxin A but not cholera toxin-mediated secreti on and permeability in a dose-dependent fashion and reduced toxin A-in duced epithelial cell damage. Rats treated with rhIL-11 also showed re duced RMCP II, TNF-alpha, and MIP-2 release in response to toxin A. Ex posure of rat peripheral monocytes in vitro to rhIL-11 (1 mu g/ml) inh ibited lipopolysaccharide and toxin A-mediated increases in TNF-alpha mRNA and protein levels. We conclude that rhIL-11 blocks the intestina l effects of C. difficile toxin A, possibly by inhibiting release of i nflammatory mediators from mucosal mast cells and intestinal macrophag es.