Secretagogue-specific effects of interleukin-1 on gastric acid secretion

Abstract

Interleukin-1 beta (IL-1 beta) has recently been shown to reduce the severity of experimental gastroduodenal damage and to inhibit acid secretion in the pylorus-ligated rat. In the present study, the effects of IL-1 beta on pentagastrin-stimulated acid secretion were compared with those of two other cytokines, namely IL-1 alpha and tumor necrosis factor (TNF) alpha. Also, the effects of IL-1 beta on gastric acid secretion stimulated by bethanechol or histamine were assessed. Anesthetized rats were pretreated intravenously with one of the cytokines, at doses in the 0.1-5 micrograms/kg range, 30 min before starting an intravenous infusion of pentagastrin. TNF alpha failed to significantly affect acid secretion, whereas IL-1 alpha and IL-1 beta exhibited significant inhibitory effects. For example, at a dose of 5 micrograms/kg, IL-1 alpha and IL-1 beta reduced acid secretion by 33 and 80%, respectively. The inhibitory effects of IL-1 beta on acid secretion could be completely inhibited by preincubation with an antibody directed against IL-1 beta but not by pretreatment with indomethacin (5 mg/kg sc) or by bilateral vagotomy. If acid secretion was stimulated by intravenous infusions of histamine or bethanechol, neither IL-1 beta nor TNF alpha produced significant inhibitory effects. Inhibition of acid secretion by IL-1 was also observed when the IL-1 was administered subsequent to stimulation by pentagastrin administration. These results demonstrate that IL-1 beta is an extremely potent inhibitor of acid secretion stimulated by pentagastrin but not that stimulated by histamine or bethanechol, through a mechanism that is at least in part independent of the vagus nerve and of prostaglandin synthesis. IL-1 alpha is less potent as an inhibitor of gastric acid secretion, whereas TNF appears to be inactive. Because pentagastrin-stimulated acid secretion could be completely inhibited by a histamine H2-receptor antagonist (cimetidine) and because IL-1 had no effect on histamine-stimulated acid secretion, it is possible that IL-1 exerts its antisecretory actions by inhibiting pentagastrin-stimulated histamine release.

Interleukin‐1B 31 C>T polymorphism combined with Helicobacter pylori‐modified gastric cancer susceptibility: evidence from 37 studies

“…On the contrary, some infected individuals with gastritis affecting the acid‐secreting corpus region might develop extensive corpus gastritis and further progressed to hypochlorhydria and gastric atrophy 56, and thereby had increased risk of gastric cancer 57, 58. It is well‐known that IL‐1β is not only an important pro‐inflammatory cytokine 3 but also a potent inhibitor of gastric acid secretion 4, 5, 59. Chang et al .…”

Interleukin‐1B (IL‐1B) polymorphisms and gastric mucosal levels of IL‐1β cytokine in Korean patients with gastric cancer

“…Both IL-1␤ and IL-1ra play a key role in modulating the inflammatory response in the gastrointestinal mucosa as well as in regulating gastric acid secretion. 18,19 The IL-1B gene has 3 diallelic polymorphisms at positions Ϫ511, Ϫ31 and ϩ3954 base pairs from the transcription start site. 32,33 The polymorphism at 3954 is not associated with the risk of GC and H. pylori infection.…”

“…15,16 However, studies on the role of genetic factors in GC risk remain inconclusive because of a number of limitations in study designs, and host factors that influence acid secretion are highly likely to influence the outcome of an H. pylori infection. Interleukin-1␤ (IL-1␤, encoded by IL-1B), a proinflammatory cytokine 17 and also a potent inhibitor of gastric acid secretion, 18 is a prime candidate in this regard. The IL-1 receptor antagonist (IL1ra, encoded by IL-1RN) is a naturally occurring antiinflammatory cytokine that modulates the potentially injurious effects of IL-1 proteins by competitively binding to the IL-1 receptor.…”

Risks of interleukin‐1 genetic polymorphisms and Helicobacter pylori infection in the development of gastric cancer

“…19 IL-1b is also a powerful inhibitor of gastric acid secretion, being 100-fold more potent than proton pump inhibitors. 20 The modulation of acid secretion and cytokine production by IL-1b may affect the outcomes of the hosts. Three diallelic polymorphisms with C-T base transitions in IL-1B have so far been reported.…”