Dose-dependent effects of recombinant human interleukin-11 on contractile properties in rabbit 2,4,6-trinitrobenzene sulfonic acid colitis.
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 microg/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 microg/kg. day rhIL-11 or saline for 5 days. Colitis affected mucosal architecture, general mechanical properties (passive tension increased with 12.3 g/mm(2), optimal stretch decreased with 26%), and collagen content (decreased from 366 +/- 25 to 237 +/- 13 microg/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 E(2) but this was normalized with 40 microg/kg. day (motilin, SP) and 720 microg/kg. day (ACh, K(+)) rhIL-11 but not for prostaglandin E(2). 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 microg/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.
Depoortere
I
I
Centre for Gastroenterological Research, Department of Pathophysiology, University of Leuven, Belgium.
Thijs
T
T
van Assche
G
G
Keith
J C
JC
Peeters
T L
TL
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D003092:Colitis / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*; D003106:Colon / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D015232:Dinoprostone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D066298:In Vitro Techniques; D017370:Interleukin-11 / Q000494:pharmacology*; D008297:Male; D009037:Motilin / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D011189:Potassium Chloride / Q000494:pharmacology; D011817:Rabbits; D011964:Receptors, Gastrointestinal Hormone / Q000378:metabolism; D018040:Receptors, Neurokinin-1 / Q000378:metabolism; D018013:Receptors, Neuropeptide / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013373:Substance P / Q000494:pharmacology; D013718:Tensile Strength; D014302:Trinitrobenzenesulfonic Acid
D017370:Interleukin-11; D011964:Receptors, Gastrointestinal Hormone; D018040:Receptors, Neurokinin-1; D018013:Receptors, Neuropeptide; D011994:Recombinant Proteins; C050802:motilin receptor; D013373:Substance P; D009037:Motilin; D011189:Potassium Chloride; D014302:Trinitrobenzenesulfonic Acid; C105308:oprelvekin; D015232:Dinoprostone; D000109:Acetylcholine