Recombinant Human Interleukin-11 Modulates Ion Transport and Mucosal Inflammation in the Small Intestine and Colon

Abstract

Human recombinant interleukin 11 (rhIL-11) is a cytokine that suppresses the clinical signs of colitis in animal models of inflammatory bowel disease (IBD) and may be an effective therapeutic agent in the treatment of IBD. The objective of the current study was to investigate whether rhIL-11 was capable of reversing abnormalities in secretomotor function associated with gut inflammation. We investigated the effects of rhIL-11 on epithelial electrogenic ion transport in the jejunum and colon. Application of rhIL-11 (10 to 10,000 ng/ml) at either the luminal or serosal side of mucosal sheets isolated from control rats induced a concentration-dependent reduction of transmural potential difference (PD) in the jejunum and decreased the short-circuit current (Isc), representative of active electrogenic transport, in the colon. To investigate the effect of rhIL-11 on an inflamed gut, we isolated jejunal and colonic tissue from HLA-B27 transgenic rats with active inflammation of the bowel that represents an animal model of IBD. In jejunum and colon isolated from HLA-B27 transgenic rats, basal electrogenic ion transport was significantly attenuated and, under these conditions, rhIL-11 caused no changes in either transmural PD or Isc. However, in HLA-B27 rats, pretreatment with subcutaneous doses of rhIL-11 suppressed the symptoms of diarrhea, normalized myeloperoxidase activity in the jejunum and colon and healed mucosal injury. In the jejunum from HLA-B27 rats, healing of the intestinal inflammatory response enhanced basal transmural PD and the rhIL-11–induced changes in mucosal ion transport resembled those seen in uninflamed controls. Conversely, in the colon, healing of the mucosa did not normalize basal active ion transport nor did it reverse the inhibition of rhIL-11–induced changes in colonic Isc. Our results suggest that endogenous IL-11 may act as a modulator of epithelial transport under physiologic conditions and may act as a potent anti-inflammatory cytokine during active intestinal inflammation.