Recombinant human interleukin-11 modulates ion transport and mucosal inflammation in the small intestine and colon

Human recombinant interleukin 11 (rhIL-11) is a cytokine that suppresses th e clinical signs of colitis in animal models of inflammatory bowel disease (IBD) and may be an effective therapeutic agent in the treatment of]BD. The objective of the current study was to investigate whether rhIL-11 was capa ble of reversing abnormalities in secretomotor function associated with gut inflammation. We investigated the effects of rhIL-11 on epithelial electro genic 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 isol ated from control rats induced a concentration-dependent reduction of trans mural potential difference (PD) in the jejunum and decreased the short-circ uit 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 HL4-B27 transgenic rats with active inflam mation of the bower that represents an animal model of IBD, in jejunum and colon isolated from HLA-B27 transgenic rats, basal electrogenic ion transpo rt was significantly attenuated and, under these conditions, rhIL-11 caused no changes in either transmural PD or Isc. However, in HLA-B27 rats, pretr eatment with subcutaneous doses of rhIL-11 suppressed the symptoms of diarr hea, normalized myeloperoxidase activity in the jejunum and colon and heale d mucosal injury. In the jejunum from HLA-B27 rats, healing of the intestin al inflammatory response enhanced basal transmural PD and the rhIL-11-induc ed changes in mucosal ion transport resembled those seen in uninflamed cont rols. Conversely, in the colon, healing of the mucosa did not normalize bas al active ion transport nor did it reverse the inhibition of rhIL-11-induce d changes in colonic Isc. Our results suggest that endogenous IL-11 may act as a modulator of epithelial transport under physiologic conditions and ma y act as a potent anti-inflammatory cytokine during active intestinal infla mmation.