Effect of genotypic differences in interleukin-1 beta on gastric acid secretion, gastric atrophy, and recurrence of peptic ulcer diseases

It has been established that interleukin-1 beta (IL-1 beta) injected into the cerebrospinal fluid inhibits gastric acid secretion in rats. Brain sites of action of IL-1 beta were investigated in conscious rats implanted unilaterally with chronic hypothalamic cannula. Gastric acid secretion was monitored 2 h after pylorus ligation. Human recombinant IL-1 beta (10 ng) microinjected into the medial preoptic area, anterior hypothalamus, and paraventricular nucleus inhibited gastric acid secretion by 76-83%. IL-1 beta microinjected into the ventromedial hypothalamus and other hypothalamic sites outside of responsive sites had no effect. IL-1 beta inhibitory action in the medial preoptic area was dose related (0.1-10 ng), prevented by indomethacin (5 mg/kg ip), and mimicked by prostaglandin E2. These results show that IL-1 beta acts in the medial preoptic area/anterior hypothalamus and paraventricular nucleus to inhibit acid secretion in pylorus-ligated rats and that IL-1 beta action is likely to involve prostaglandin E2.

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Interleukin-1 beta inhibits gastric histamine secretion and synthesis in the rat

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1994.267.6.g966 ◽

1994 ◽

Vol 267 (6) ◽

pp. G966-G971 ◽

Cited By ~ 2

Author(s):

S. Kondo ◽

Y. Shinomura ◽

S. Kanayama ◽

S. Kawabata ◽

Y. Miyazaki ◽

...

Keyword(s):

Acid Secretion ◽

Gastric Acid Secretion ◽

Gastric Acid ◽

Histidine Decarboxylase ◽

Interleukin 1 ◽

Interleukin 1 Beta ◽

Inhibitory Effects ◽

Histamine Secretion ◽

Basal Acid ◽

Urinary Histamine

Interleukin-1 beta (IL-1 beta) is the most potent inhibitor of gastric acid secretion known at present. Although histamine has been shown to be an important mediator of gastric acid secretion, the effect of IL-1 beta on gastric histamine mobilization has not been studied. In the present study, the effects of IL-1 beta on gastric acid secretion and gastric histamine mobilization were investigated in conscious rats with both gastric and vesical fistulas. IL-1 beta (5 micrograms/kg iv) significantly inhibited basal acid secretion but did not affect basal urinary histamine excretion and fundic histidine decarboxylase (HDC) activity. Gastrin-17-I (1 nmol.kg-1.h-1) caused a marked increase in acid secretion, urinary histamine secretion, and fundic HDC activity. IL-1 beta (5 micrograms/kg iv) completely inhibited gastrin-induced acid secretion and partially inhibited urinary histamine excretion and fundic HDC activity. Pretreatment with indomethacin (10 mg/kg ip) partially reversed the inhibitory effects of IL-1 beta on gastrin-stimulated fundic HDC activity and acid secretion. These findings indicate that IL-1 beta inhibits gastric histamine mobilization through both prostaglandin-dependent and prostaglandin-independent pathways. Furthermore, it is suggested that the inhibitory action of IL-1 beta on gastric acid secretion is mediated by the inhibition of gastric histamine mobilization.

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The Predictive Value of Cimetidine-Induced Inhibition of Gastric Acid Secretion on the Outcome of Treatment in Peptic Ulcer Disease

Scandinavian Journal of Gastroenterology ◽

10.1080/00365521.1984.12005785 ◽

1984 ◽

Vol 19 (5) ◽

pp. 639-642 ◽

Cited By ~ 4

Author(s):

M. Ström ◽

G. Bodemar ◽

B. Norlander ◽

A. Walan

Keyword(s):

Peptic Ulcer ◽

Acid Secretion ◽

Peptic Ulcer Disease ◽

Gastric Acid Secretion ◽

Gastric Acid ◽

Predictive Value ◽

Ulcer Disease

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The Role of Gastric Acid in Preventing Foodborne Disease and How Bacteria Overcome Acid Conditions†

Journal of Food Protection ◽

10.4315/0362-028x-66.7.1292 ◽

2003 ◽

Vol 66 (7) ◽

pp. 1292-1303 ◽

Cited By ~ 126

Author(s):

JAMES L. SMITH

Keyword(s):

Peptic Ulcer ◽

Acid Secretion ◽

Peptic Ulcer Disease ◽

Gastric Acid Secretion ◽

Gastric Acid ◽

Gastric Fluid ◽

The Body ◽

Peptic Ulcers ◽

Ulcer Disease ◽

H Pylori

The secretion of hydrochloric acid by the stomach plays an important role in protecting the body against pathogens ingested with food or water. A gastric fluid pH of 1 to 2 is deleterious to many microbial pathogens; however, the neutralization of gastric acid by antacids or the inhibition of acid secretion by various drugs may increase the risk of food- or waterborne illnesses. Peptic ulcer disease is often treated by decreasing or eliminating gastric acid secretion, and such treatment blocks the protective antibacterial action of gastric fluid. The majority of peptic ulcer disease cases originate from Helicobacter pylori infections. Treatment of H. pylori–induced peptic ulcers with antibiotics reduces the need for drugs that inhibit gastric acid secretion and thereby diminishes the risk of food- and waterborne illness for peptic ulcer disease patients. Many bacterial pathogens, such as Escherichia coli, Salmonella Typhimurium, and H. pylori, can circumvent the acid conditions of the stomach by developing adaptive mechanisms that allow these bacteria to survive in acid environments. As a consequence, these bacteria can survive acidic stomach conditions and pass into the intestinal tract, where they can induce gastroenteritis.

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

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1991.261.4.g559 ◽

1991 ◽

Vol 261 (4) ◽

pp. G559-G564 ◽

Cited By ~ 17

Author(s):

J. L. Wallace ◽

M. Cucala ◽

K. Mugridge ◽

L. Parente

Keyword(s):

Acid Secretion ◽

Gastric Acid Secretion ◽

Gastric Acid ◽

Interleukin 1 ◽

Tnf Alpha ◽

Inhibitory Effects ◽

H2 Receptor Antagonist ◽

Histamine H2 Receptor ◽

Specific Effects ◽

Bilateral Vagotomy

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.

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