Abstract

We studied the effect of recombinant human interleukin-11 (rhIL-11), a cytokine with protective effects against injury to the intestinal mucosa, on inflammatory changes in the muscle layers of the gut, in rabbits with colitis. A single dose of rhIL-11 (4, 40, or 720 μg/kg) was given 1 h before colitis was induced with 135 mg/kg 2,4,6-trinitrobenzene sulfonic acid (TNBS), followed by a continuous s.c. administration of 4, 40, or 720 μg/kg · day rhIL-11 or saline for 5 days. Colitis affected mucosal architecture, general mechanical properties (passive tension increased with 12.3 g/mm², optimal stretch decreased with 26%), and collagen content (decreased from 366 ± 25 to 237 ± 13 μg/mg of protein). Changes in passive tension and collagen content were normalized by the highest and lowest dose of rhIL-11, respectively, but neither dose could normalize the optimal stretch. Colitis also decreased maximal contractile tension in response to acetylcholine (ACh), motilin, substance P (SP), K⁺, and prostaglandin E₂ but this was normalized with 40 μg/kg · day (motilin, SP) and 720 μg/kg · day (ACh, K⁺) rhIL-11 but not for prostaglandin E₂. For motilin and SP, receptor density was decreased in colitis and normalized in treated rabbits. Colitis also increased the contractile potency toward ACh, an effect already reversed by rhIL-11, 4 μg/kg · day. In conclusion, rhIL-11 partially normalizes disturbed tension generation in experimental colitis. The use of this cytokine in the treatment of irritable bowel disease may contribute to the restoration of motor dysfunction.