Gastric antisecretory and antiulcer actions of interleukin-1. Evidence for the presence of an "immune-brain-gut" axis.
Increasing evidence suggests that interleukin-1 (IL-1), a cytokine mainly produced by activated monocytes/macrophages, has various biological actions in addition to its immunological activities. In the present study, we examined the effect of IL-1 on gastric secretion and gastric ulcer formation in rats. Gastric secretion was assessed in conscious pylorus-ligated rats weighing approximately 200 g. The peripheral injection of IL-1 resulted in a dose-related inhibition of gastric acid output. The central injection of IL-1 similarly reduced gastric acid secretion at 100 times smaller doses than peripherally injected IL-1, suggesting that this gastric antisecretory action of IL-1 is mediated by the central nervous system. In addition, it was found that this inhibitory effect of IL-1, either peripherally or centrally administered, was still evident at 8 h after injection, indicating the long-lasting property of this IL-1 action. On the basis of these antisecretory actions of IL-1, we determined whether or not pretreatment with IL-1 would prevent experimentally induced gastric ulcer formation. As expected, the central administration of IL-1 dose-dependently suppressed the development of gastric mucosal lesions induced by water-immersion restraint stress, a well-established ulcerogenic procedure. These results clearly demonstrated that IL-1 has potent antisecretory and antiulcer effects that are mediated by the central nervous system. Moreover, these findings suggest that there may exist an "immune-brain-gut" axis, which is involved in the regulation of gastric secretion and mucosal homeostasis, especially under certain pathophysiological conditions that activate the immune system to release various cytokines including IL-1.
Uehara
A
A
Department of Internal Medicine (III), Asahikawa Medical College, Hokkaido, Japan.
Okumura
T
T
Kitamori
S
S
Shibata
Y
Y
Harada
K
K
Okamura
K
K
Takasugi
Y
Y
Namiki
M
M
D000818:Animals; D001921:Brain / Q000276:immunology / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D005744:Gastric Acid / Q000378:metabolism*; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism; D006706:Homeostasis / Q000187:drug effects; D007375:Interleukin-1 / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D008954:Models, Biological; D010434:Pepsin A / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013276:Stomach Ulcer / Q000209:etiology / Q000276:immunology / Q000517:prevention & control*; D013312:Stress, Physiological / Q000150:complications
D007375:Interleukin-1; D010434:Pepsin A