Inhibition of Gastric Acid Secretion by Bacterial Lipopolysaccharide

Abstract

Baume, Nicholls and Baxter report the potent effect of lipopolysaccharide on gastric secretion as if this were a uew observation 1 • But, the effect was clearly described in 1950 (ref. 2). We have made similar experiments in conscious dogs with vagally denervated pouches of the body of the stomach. Gastric secretion was stimulated by a low dose of histamine given by constant intravenous infusion (100 [Lg/h of histamine base).Gastric acid secretion was abolished by doses of IO [Lg/kg of Pseudomonas polysaccharide pyrogen ('Piromen', Flint Laboratories Inc.) given intravenously over a period of about :lO min during stimulation with histamine. Secretion failed progressively over 2-3 h during which time tho dogs developed pyrexia as indicated by a thermistor in the rectum (Fig. 1). In control experiments in which saline was given in place of 'Piromen' secretion was maintained.When gastric acid secretion is stimulated in conscious dogs by feeding, by intravenous 2-deoxy-n-glucose, or by gastrin infusion, atropine sulphate (0•1 mg/kg intravenously) practically abolishes the secretion.Under similar conditions secretion stimulated by histamine is ,•irtually unaffected 3 • Also, secretion stimulated by histamine is much more resistant to depression caused by devation of the plasma calcium concentration than is Hccretion stimulated by gastrin•. From this we deduce that histamine acts, as is generally supposed, directly on the secreting cells. The potent action of lipopolysaccharide against secretion stimulated by histamine is therefore likely to reflect an effect on the secretory mechanism and not on intrinsic or extrinsic nerves. We agree with Baume et aU that alterations in gastric blood flow could be responsible for the effect.The slow development of inhibition of secretion in our ex:periments~it seemed to run parallel with rise in body temperaturc~suggcsts that inhibition of secretion, like pyrexia, depends on development of a mediator such as leucocyte bacterial pyrogen•. It should, however, be mentioned that it has been claimed that in rats lipopoly-879 saccharide has gastric secretory inhibitory activity unrelated to its pyrexic effect•.The significance of these observations is two-fold: first, the potency of bacterial lipopolysaccharide in inhibiting gastric secretion merits further investigation: and second, gastric secretory inhibition by biological extracts and other substances should always be accompanied by temperature recordings over several hours.

Effect of Purified Lipopolysaccharides from Strains of Helicobacter pylori and Helicobacter felis on Acid Secretion in Mouse Gastric Glands In Vitro

“…In the present study, only LPS of the Sydney strain of H. pylori caused direct stimulation of acid secretion, whereas the other tested preparations did not cause any significant change in acid secretion. A number of earlier reports have shown that LPS from gram-negative bacteria was able to inhibit acid secretion in vivo (1,28,32). In particular, these reports focused on the effect of E. coli-derived LPS, and its in vivo inhibitory effect has remained undisputed.…”

“…The presence of Helicobacter infection can modulate acid secretion by altering the physiology of G cells, D cells, and parietal cells (7). It can do this either by the direct presence of its metabolites or through induction of the inflammatory process as mediated by a wide range of cytokines.Gram-negative bacterial lipopolysaccharide (LPS) from a number of bacterial species effectively inhibits gastric acid secretion in vivo (1,6,26,28,32). However, the mechanism of LPS action suggests the involvement of inflammatory products or mediators such as cytokines and prostaglandins (25,27).…”

Relationship between gastric secretion and infection.

“…In conscious dogs with denervated gastric pouches, histamine stimulated acid secretion was abolished by the intravenous administration of a lipopolysaccharide derived from Pseudomonas aeruginosa. 87 Substances, which are also probably lipopolysaccharides, have been isolated from the cultures of Streptomyces bottropensis and Bacillus subtilis which suppress acid secretion in rats and reduce the incidence of stress ulcers.88 89 Less is known about the effects of viral infection on gastric secretion. There is evidence from experiments on rabbits that certain viruses, however, particularly Vaccinia, are associated with the production of an oligopeptide in the host which can inhibit acid secretion, and which suppresses acid output when administered to other animals.9"…”

Inhibition of gastric secretion by bacterial lipopolysaccharide in the rat

“…This has been shown in the dog (Blickenstaff and Grossman, 1950;Wyllie et al, 1967) and in the rat (Olson et al, 1954;Brodie and Kundrats, 1964;Baume et al, 1967).…”