Effect of interleukin-1beta on the ascending and descending reflex in rat small intestine

Acute inflammation of the intestine is associated with motility changes. We investigated the acute effect of inflammatory mediators such as interleukin-1beta, interleukin-2 and tumor necrosis factor-alpha (TNF-alpha) on electrically stimulated ascending and descending reflex responses of the rat small intestine. Exogenous application of interleukin-1beta caused a concentration-dependent inhibition of the oral contraction (0.1 ng/ml: -22.9+/-3.8%, 10 ng/ml: -57.0+/-7.4%, P < 0.05, n=10) but had no effect on anal relaxation. The interleukin-1 receptor antagonist alone had no significant effect on the reflex response, but prevented the inhibitory effect of interleukin-1beta (10 ng/ml: -3.9+/-11.4%, n=8). Interleukin-2 and TNF-alpha had no significant effect on the oral contractile and the anal inhibitory response (n.s., n=10). Using reverse transcriptase polymerase chain reaction (RT-PCR) the presence of mRNA of the interleukin-1 receptor was demonstrated in the rat small intestine. Preincubation of the preparation with indomethacin (10(-6) M), the histamine H1 receptor antagonist, pyrilamine (10(-8) M), and the histamine H3 receptor antagonist, clobenpropit (10(-8) M), decreased the oral contraction by 60.1+/-7.7%, 42.8+/-6.9% and 44.4+/-14.2% as well as the anal relaxation. These data suggest that acute administration of interleukin-1beta inhibits the ascending and descending contractile reflex pathway and this effect seems not to be mediated by prostaglandins or histamine receptors.