Effect of recombinant human interleukin-11 on motilin and substance P release in normal and inflamed rabbits

Recombinant human interleukin-11 (rhIL-11) normalizes depressed smooth musc le tension generation towards motilin and substance P (SP) in rabbits with colitis. The aim of this paper was to evaluate the effect of rhIL-11 treatm ent on motilin and SP release which could have an effect on the contractili ty changes. Rabbits received 4, 40, 72 or 720 mug/kg rhIL-11 s.c. or saline , 1 h later a continuous s.c. administration of rhIL-11 was started with or without the induction of colitis (135 mg/kg TNBS) for 5 days. Motilin and SP levels were measured by RIA, motilin mRNA expression by RT-PCR. TNBS-col itis did not affect plasma motilin levels but increased the motilin content of the duodenal mucosa 1.7-fold. rhIL-11 treatment dose-dependently increa sed plasma motilin levels (720 mug/kg day: 3.5-fold) and the motilin conten t of the duodenal mucosa (720 mug/kg day: 3.0-fold). The effects of rhIL-11 were similar in normal rabbits and were accompanied by an increased motili n mRNA expression. TNBS-colitis decreased plasma SP levels 2.7-fold and the SP content in the colonic muscle layer 7.1-fold. The decrease in the muscl e layer, but not in the plasma, was normalized by rhIL-11 treatment. In nor mal rabbits, rhIL-11 caused a decrease in plasma SP levels, but had no effe ct on the tissue content of SP. In conclusion, treatment of inflamed or nor mal rabbits with rhIL-11 increases plasma and tissue levels of motilin in t he duodenal mucosa via an increased expression of motilin in the endocrine cells and induces the release of SP from extrinsic neurons. These changes d o not explain the beneficial effect of rhIL-11 on the lowered contractility in inflamed rabbits although a change in balance of neuropeptides may infl uence gastro-intestinal inflammation. (C) 2001 Elsevier Science B.V. All ri ghts reserved.