Interleukin 1β and tumour necrosis factor α inhibit acid secretion in cultured rabbit parietal cells by multiple pathways

Abstract

Background-The cytokines interleukin 1 (IL-1 ) and tumour necrosis factor (TNF-) are inhibitors of gastric acid secretion when administered systemically. Aims-To investigate the inhibitory eVect of IL-1 and TNF-on cultured, acid secreting parietal cells in order to determine the mechanism of this inhibition. Methods-Rabbit parietal cells were prepared by collagenase-EDTA digestion and counter flow elutriation. Acid secretory activity was assessed by aminopyrine accumulation. Results-IL-1 and TNF-inhibited basal and stimulated acid secretion in a dose dependent manner; near maximal eVects were seen with both at 10 ng/ml. Inhibition was maximal with 15 minutes pretreatment but seen with up to 18 hours of preincubation. Both cytokines inhibited histamine, carbachol, gastrin, forskolin, and A23187 stimulated acid secretion but had no eVect on stimulation by dibutyrylcAMP. Inhibition of acid secretion was not accompanied by a change in radioligand binding to histamine H 2 or gastrin/CCK B receptors. Pertussis toxin abolished the inhibitory eVects on histamine and forskolin stimulation. The tyrosine kinase inhibitor herbimycin reduced the inhibitory eVects of TNF-against all stimuli but only reduced the eVects of IL-1 against histamine and forskolin stimulation. Conclusions-IL-1 and TNF-seem to inhibit parietal cell acid secretion by multiple pathways; the inhibition occurs at postreceptor level and involves pertussis toxin and tyrosine kinase dependent and independent pathways. Mucosal production of cytokines may be important in the regulation of gastric acid secretion. (Gut 1998;42:227-234)

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 .…”

IL1RN polymorphic gene and cagA‐positive status independently increase the risk of noncardia gastric carcinoma

“…Furthermore, IL-1b is a powerful gastric acid inhibitor and increased gastric levels of IL-1b may cause hypochlorhydria. 16 The IL1RN gene has a variable number of tandem repeats in intron 2, resulting in a short allele (IL1RN2) with 2 repeats or long alleles (IL1RN1) with 3-6 repeats. The IL1RN2 allele is also associated with increased IL-1b production, severe gastric lesions and increased risk for gastric carcinoma.…”

Subjects with TNF-A-857TT and -1031TT genotypes showed the highest Helicobacter pylori seropositive rate compared with those with other genotypes

“…Tumor necrosis factor (TNF)-α is a cytokine induced by H. pylori [11], and inhibits gastric acid secretion [12]. The TNF-A gene on chromosome 6p21.3 encoding TNF-α is known to have five biallelic single-nucleotide polymorphisms in the promoter region; G-238A, G-308A, C-857T, C-863A, and T-1031C [13].…”