Central action of recombinant interleukin-1 to inhibit acid secretion in rats

Gastroenterology. 1990 Dec;99(6):1599-606. doi: 10.1016/0016-5085(90)90463-b.


The influence of recombinant human interleukins-1 beta and -1 alpha and rat interleukin-1 beta on gastric acid secretion was investigated in awake rats with pylorus ligation. IC injection of either human interleukin-1 beta, human interleukin-1 alpha, or rat interleukin-1 beta induced a dose-dependent inhibition of gastric acid output. At IC doses less than 100 ng, human interleukin-1 beta was more effective than the other forms or sources of interleukin-1, whereas at higher doses (100-500 ng), human interleukins-1 beta and -1 alpha and rat interleukin-1 beta were equipotent. The inhibitory effect was observed 30 minutes after interleukin-1 injection and maintained throughout the 6-hour experimental period. IC injection of interleukin-1 beta inhibited vagally stimulated gastric acid secretion induced by IC injection of the stable thyrotropin-releasing hormone analogue RX 77368. Indomethacin (1, 5, and 10 mg/kg, IP, -30 minutes) induced a dose-related prevention of the inhibitory effect of IC interleukin-1 beta. IC injection of the corticotropin-releasing factor antagonist alpha-CRF9-41, bilateral adrenalectomy, and noradrenergic blockade with bretylium did not influence the antisecretory effect of interleukin-1. Polypeptide action was not related to changes in circulating gastrin levels. Human interleukin-1 beta injected IV also inhibited gastric acid secretion, but the peripheral dose required to induce a significant effect was 10(3)-fold higher than when given centrally. These results show that IC interleukin-1 beta acts centrally to induce a long-lasting inhibition of gastric acid secretion, and this effect requires the integrity of prostaglandin pathways. These data suggest a possible interaction between the immune and gastrointestinal systems.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Brain / physiology*
  • Dose-Response Relationship, Drug
  • Gastric Acid / metabolism*
  • Indomethacin / pharmacology
  • Injections
  • Injections, Intraperitoneal
  • Interleukin-1 / pharmacology*
  • Male
  • Pyrrolidonecarboxylic Acid / analogs & derivatives
  • Rats
  • Rats, Inbred Strains
  • Recombinant Proteins
  • Thyrotropin-Releasing Hormone / analogs & derivatives
  • Thyrotropin-Releasing Hormone / pharmacology


  • Interleukin-1
  • Recombinant Proteins
  • Thyrotropin-Releasing Hormone
  • L-pyroglutamyl-L-histidyl-3,3-dimethylprolinamide
  • Pyrrolidonecarboxylic Acid
  • Indomethacin