Skip to main content
PMC home page
Gut logoLink to Gut
. 1989 Sep;30(9):1270–1274. doi: 10.1136/gut.30.9.1270

Prostaglandin E2 and leukotriene B4 synthesis by peripheral leucocytes in alcoholics.

W J Maxwell 1, J J Keating 1, F P Hogan 1, N P Kennedy 1, P W Keeling 1
PMCID: PMC1434254  PMID: 2553553

Abstract

Alcohol inhibits phospholipase (PL) activity in a number of animal models. We have therefore measured prostaglandin E2 (PGE2) and leukotriene B4 (LTB4), liberated by stimulated peripheral blood mononuclear cells (PBMC) and neutrophils respectively in chronic alcoholics and in control subjects. Peripheral blood mononuclear cells from alcoholics produced less PGE2 (p less than 0.01) and neutrophils produced less LTB4 (p less than 0.025). Reduced PGE2 production by PBMC of alcoholics was corrected by the addition of exogenous arachidonic acid (p less than 0.005) whilst neutrophil LTB4 production remained lower in the alcoholics (p less than 0.01). Percutaneous liver biopsies were undertaken in the 20 alcoholics having abnormal liver function tests. Prostaglandin E2 biosynthesis was lower in PBMC from patients with alcoholic hepatitis than with alcoholic cirrhosis (p less than 0.05). Analysis of PBMC fatty acid composition demonstrated that endogenous arachidonate and linoleate contents were not significantly different in alcoholics and controls. Cells from controls and alcoholics were incubated with 0, 50 and 150 mmol/l ethanol for two hours but there was no alteration in PGE2 or LTB4 biosynthesis. In summary, we found reduced eicosanoid production by peripheral leucocytes in alcoholics, supporting the hypothesis that chronic alcohol consumption either inhibits membrane bound phospholipase activity or enhances, alternatively, catabolism of eicosanoids. This phenomenon is more marked in alcoholic patients with hepatitis than in those with cirrhosis alone.

Full text

PDF
1274

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Berridge M. J. Inositol trisphosphate and diacylglycerol as second messengers. Biochem J. 1984 Jun 1;220(2):345–360. doi: 10.1042/bj2200345. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Crofton R. W., Diesselhoff-den Dulk M. M., van Furth R. The origin, kinetics, and characteristics of the Kupffer cells in the normal steady state. J Exp Med. 1978 Jul 1;148(1):1–17. doi: 10.1084/jem.148.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Decker K. Eicosanoids, signal molecules of liver cells. Semin Liver Dis. 1985 May;5(2):175–190. doi: 10.1055/s-2008-1063921. [DOI] [PubMed] [Google Scholar]
  4. Ford-Hutchinson A. W., Bray M. A., Doig M. V., Shipley M. E., Smith M. J. Leukotriene B, a potent chemokinetic and aggregating substance released from polymorphonuclear leukocytes. Nature. 1980 Jul 17;286(5770):264–265. doi: 10.1038/286264a0. [DOI] [PubMed] [Google Scholar]
  5. Goodwin J. S., Webb D. R. Regulation of the immune response by prostaglandins. Clin Immunol Immunopathol. 1980 Jan;15(1):106–122. doi: 10.1016/0090-1229(80)90024-0. [DOI] [PubMed] [Google Scholar]
  6. Guarner F., Fremont-Smith M., Prieto J. Cytoprotective effect of prostaglandins on isolated rat liver cells. Liver. 1985 Feb;5(1):35–39. doi: 10.1111/j.1600-0676.1985.tb00013.x. [DOI] [PubMed] [Google Scholar]
  7. Harris R. A., Fenner D. [Ethanol and synaptosomal calcium binding]. Biochem Pharmacol. 1982 May 1;31(9):1790–1792. doi: 10.1016/0006-2952(82)90688-8. [DOI] [PubMed] [Google Scholar]
  8. Johnson R. D., Williams R. Genetic and environmental factors in the individual susceptibility to the development of alcoholic liver disease. Alcohol Alcohol. 1985;20(2):137–160. [PubMed] [Google Scholar]
  9. Keppler D., Hagmann W., Rapp S., Denzlinger C., Koch H. K. The relation of leukotrienes to liver injury. Hepatology. 1985 Sep-Oct;5(5):883–891. doi: 10.1002/hep.1840050530. [DOI] [PubMed] [Google Scholar]
  10. Lelbach W. K. Cirrhosis in the alcoholic and its relation to the volume of alcohol abuse. Ann N Y Acad Sci. 1975 Apr 25;252:85–105. doi: 10.1111/j.1749-6632.1975.tb19146.x. [DOI] [PubMed] [Google Scholar]
  11. Ohnishi S. T., Obzansky D. M., Price H. L. The increase in calcium binding of cardiac plasma membrane lipoprotein caused by general anesthetics and alcohol. Can J Physiol Pharmacol. 1980 May;58(5):525–530. doi: 10.1139/y80-086. [DOI] [PubMed] [Google Scholar]
  12. Peers S. H., Hoult J. R. Inhibition by ethanol and mepacrine of phospholipase-dependent prostaglandin release from the isolated perfused rat lung. Eur J Pharmacol. 1986 Jan 21;120(2):145–150. doi: 10.1016/0014-2999(86)90534-0. [DOI] [PubMed] [Google Scholar]
  13. Rasmussen H. The calcium messenger system (2). N Engl J Med. 1986 May 1;314(18):1164–1170. doi: 10.1056/NEJM198605013141807. [DOI] [PubMed] [Google Scholar]
  14. Salmon J. A., Simmons P. M., Palmer R. M. A radioimmunoassay for leukotriene B4. Prostaglandins. 1982 Aug;24(2):225–235. doi: 10.1016/0090-6980(82)90148-4. [DOI] [PubMed] [Google Scholar]
  15. Scott J. A. Phospholipase activity and plasma membrane homeostasis. J Theor Biol. 1984 Dec 21;111(4):659–665. doi: 10.1016/s0022-5193(84)80260-x. [DOI] [PubMed] [Google Scholar]
  16. Vanderhoek J. Y., Bryant R. W., Bailey J. M. Regulation of leukocyte and platelet lipoxygenases by hydroxyeicosanoids. Biochem Pharmacol. 1982 Nov 1;31(21):3463–3467. doi: 10.1016/0006-2952(82)90627-x. [DOI] [PubMed] [Google Scholar]
  17. Vincenzi F. F., Larsen F. L. The plasma membrane calcium pump: regulation by a soluble Ca2+ binding protein. Fed Proc. 1980 May 15;39(7):2427–2431. [PubMed] [Google Scholar]
  18. Williamson J. R., Cooper R. H., Joseph S. K., Thomas A. P. Inositol trisphosphate and diacylglycerol as intracellular second messengers in liver. Am J Physiol. 1985 Mar;248(3 Pt 1):C203–C216. doi: 10.1152/ajpcell.1985.248.3.C203. [DOI] [PubMed] [Google Scholar]
  19. Yam L. T., Li C. Y., Crosby W. H. Cytochemical identification of monocytes and granulocytes. Am J Clin Pathol. 1971 Mar;55(3):283–290. doi: 10.1093/ajcp/55.3.283. [DOI] [PubMed] [Google Scholar]

Articles from Gut are provided here courtesy of BMJ Publishing Group

RESOURCES