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.
Footnotes
-
Send reprint requests to: Theo L. Peeters, Centre for Gastroenterological Research, Gasthuisberg O & N, B-3000 Leuven, Belgium. E-mail: theo.peeters{at}med.kuleuven.ac.be
-
↵1 This study was supported by grants from the Fund for Scientific Research-Flanders (Belgium) (FWO Grant G 0109.00) and the Belgian Ministry of Science (GOA 98/011 and IUAP P4/16). I.D. is a postdoctoral research fellow of the Fund for Scientific Research-Flanders. This work has been presented at the American Gastroenterological Association in New Orleans (Depoortere et al., 1998).
- Abbreviations:
- IL
- interleukin
- TNF-α
- tumor necrosis factor-α
- TNBS
- 2,4,6-trinitrobenzene sulfonic acid
- CD
- Crohn's disease
- rhIL-11
- recombinant human interleukin-11
- ACh
- acetylcholine
- SP
- substance P
- PGE2
- prostaglandin E2
- IBD
- irritable bowel disease
- IL-RA
- interleukin receptor antagonist
- COX-2
- cyclooxygenase-2
- PCR
- polymerase chain reaction
- GAPDH
- glyceraldehyde-3-phosphate dehydrogenase
- UC
- ulcerative colitis
- NK
- neurokinin
- Received January 21, 2000.
- Accepted May 2, 2000.
- The American Society for Pharmacology and Experimental Therapeutics
JPET articles become freely available 12 months after publication, and remain freely available for 5 years.Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page.
|