Leukemia inhibitory factor mediates cytokine-induced suppression of myenteric neurotransmitter release from rat intestine.
OBJECTIVE
Exposure of rat longitudinal muscle myenteric plexus to the proinflammatory cytokine interleukin (IL) 1 beta mimics the effects of nematode infection on enteric nerve function through a hitherto unidentified protein intermediate. It is postulated that leukemia inhibitory factor (LIF), the downstream intermediate of several IL-1-induced neuroimmune interactions, mediates IL-1 beta-induced suppression of acetylcholine release from rat jejunum.


METHODS
Preparations were preloaded with [3H]choline, and [3H]-acetylcholine release was induced by either electrical field stimulation or by 50 mmol/L KCl. Cytokines and anti-LIF antibodies were added to the preincubation media or to the superfusate before stimulation.


RESULTS
Human recombinant LIF had no immediate effects, but preincubation with the cytokine induced a concentration-dependent (2-100 ng/mL) and reversible suppression of acetylcholine release from rat longitudinal muscle myenteric plexus. The effects of human recombinant LIF on acetylcholine release were reversed by anti-human recombinant LIF-neutralizing antibody. Human recombinant IL-1 beta (10 ng/mL) induced a similar suppression of acetylcholine release, and the addition of anti-rat LIF antibody abolished the effects of exogenous IL-1 on acetylcholine release.


CONCLUSIONS
IL-1 beta suppresses neurotransmitter release from rat myenteric plexus via the induction of LIF as a downstream intermediate.
Van Assche
G
G
Intestinal Diseases Research Programme, McMaster University, Hamilton, Ontario, Canada.
Collins
S M
SM
D000109:Acetylcholine / Q000037:antagonists & inhibitors; D000818:Animals; D016207:Cytokines / Q000494:pharmacology*; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism*; D008222:Lymphokines / Q000494:pharmacology / Q000502:physiology*; D008297:Male; D009130:Muscle, Smooth / Q000378:metabolism; D009197:Myenteric Plexus / Q000378:metabolism*; D018377:Neurotransmitter Agents / Q000037:antagonists & inhibitors*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins; D014316:Tritium
D016207:Cytokines; D008222:Lymphokines; D018377:Neurotransmitter Agents; D011994:Recombinant Proteins; C010598:leukocyte inhibitory factor; D014316:Tritium; D000109:Acetylcholine