Skip to main content
Gut logoLink to Gut
. 1991 Dec;32(12):1473–1477. doi: 10.1136/gut.32.12.1473

Mucosal tumour necrosis factor alpha and interleukin-6 in patients with Helicobacter pylori associated gastritis.

J E Crabtree 1, T M Shallcross 1, R V Heatley 1, J I Wyatt 1
PMCID: PMC1379245  PMID: 1773951

Abstract

The production of tumour necrosis factor alpha (TNF alpha) and interleukin-6 by human antral mucosa during short term culture in vitro has been measured by enzyme linked immunosorbent assay. TNF alpha and interleukin-6 concentrations in culture supernatants were significantly greater (p less than 0.001) in patients infected with Helicobacter pylori, all of whom had chronic gastritis, than in patients who were H pylori negative with histologically normal gastric mucosa. Among H pylori colonised patients, TNF alpha concentrations were significantly higher in those with active gastritis and neutrophil infiltration into the epithelium than in those with inactive gastritis. In contrast, interleukin-6 concentrations were raised in both active and inactive gastritis. This study shows that H pylori gastritis is associated with increased gastric mucosal production of TNF alpha and interleukin-6 and that the nature of the mucosal cytokine response varies with the immunohistology of the disease. Inflammatory cytokines generated locally within the gastric mucosa could be relevant to the gastric physiology of H pylori infection.

Full text

PDF
1473

Selected References

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

  1. Bate C. A., Taverne J., Playfair J. H. Malarial parasites induce TNF production by macrophages. Immunology. 1988 Jun;64(2):227–231. [PMC free article] [PubMed] [Google Scholar]
  2. Bate C. A., Taverne J., Playfair J. H. Soluble malarial antigens are toxic and induce the production of tumour necrosis factor in vivo. Immunology. 1989 Apr;66(4):600–605. [PMC free article] [PubMed] [Google Scholar]
  3. Beutler B., Cerami A. The biology of cachectin/TNF--a primary mediator of the host response. Annu Rev Immunol. 1989;7:625–655. doi: 10.1146/annurev.iy.07.040189.003205. [DOI] [PubMed] [Google Scholar]
  4. Bhardwaj N., Santhanam U., Lau L. L., Tatter S. B., Ghrayeb J., Rivelis M., Steinman R. M., Sehgal P. B., May L. T. IL-6/IFN-beta 2 in synovial effusions of patients with rheumatoid arthritis and other arthritides. Identification of several isoforms and studies of cellular sources. J Immunol. 1989 Oct 1;143(7):2153–2159. [PubMed] [Google Scholar]
  5. Borish L., Rosenbaum R., Albury L., Clark S. Activation of neutrophils by recombinant interleukin 6. Cell Immunol. 1989 Jul;121(2):280–289. doi: 10.1016/0008-8749(89)90026-9. [DOI] [PubMed] [Google Scholar]
  6. Crabtree J. E., Heatley R. V., Losowsky M. S. Glycoprotein synthesis and secretion by cultured small intestinal mucosa in coeliac disease. Gut. 1989 Oct;30(10):1339–1343. doi: 10.1136/gut.30.10.1339. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Danis V. A., Harries A. D., Heatley R. V. In vitro immunoglobulin secretion by normal human gastrointestinal mucosal tissues, and alterations in patients with inflammatory bowel disease. Clin Exp Immunol. 1984 Apr;56(1):159–166. [PMC free article] [PubMed] [Google Scholar]
  8. Ferrante A., Nandoskar M., Walz A., Goh D. H., Kowanko I. C. Effects of tumour necrosis factor alpha and interleukin-1 alpha and beta on human neutrophil migration, respiratory burst and degranulation. Int Arch Allergy Appl Immunol. 1988;86(1):82–91. doi: 10.1159/000234610. [DOI] [PubMed] [Google Scholar]
  9. Fong Y., Moldawer L. L., Marano M., Wei H., Tatter S. B., Clarick R. H., Santhanam U., Sherris D., May L. T., Sehgal P. B. Endotoxemia elicits increased circulating beta 2-IFN/IL-6 in man. J Immunol. 1989 Apr 1;142(7):2321–2324. [PubMed] [Google Scholar]
  10. Helfgott D. C., Tatter S. B., Santhanam U., Clarick R. H., Bhardwaj N., May L. T., Sehgal P. B. Multiple forms of IFN-beta 2/IL-6 in serum and body fluids during acute bacterial infection. J Immunol. 1989 Feb 1;142(3):948–953. [PubMed] [Google Scholar]
  11. Isaacson P. Immunoperoxidase study of the secretory immunoglobulin system and lysozyme in normal and diseased gastric mucosa. Gut. 1982 Jul;23(7):578–588. doi: 10.1136/gut.23.7.578. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Jablons D. M., Mulé J. J., McIntosh J. K., Sehgal P. B., May L. T., Huang C. M., Rosenberg S. A., Lotze M. T. IL-6/IFN-beta-2 as a circulating hormone. Induction by cytokine administration in humans. J Immunol. 1989 Mar 1;142(5):1542–1547. [PubMed] [Google Scholar]
  13. Jirik F. R., Podor T. J., Hirano T., Kishimoto T., Loskutoff D. J., Carson D. A., Lotz M. Bacterial lipopolysaccharide and inflammatory mediators augment IL-6 secretion by human endothelial cells. J Immunol. 1989 Jan 1;142(1):144–147. [PubMed] [Google Scholar]
  14. Kharazmi A., Nielsen H., Rechnitzer C., Bendtzen K. Interleukin 6 primes human neutrophil and monocyte oxidative burst response. Immunol Lett. 1989 May;21(2):177–184. doi: 10.1016/0165-2478(89)90056-4. [DOI] [PubMed] [Google Scholar]
  15. Kishimoto T. The biology of interleukin-6. Blood. 1989 Jul;74(1):1–10. [PubMed] [Google Scholar]
  16. Kohase M., Henriksen-DeStefano D., May L. T., Vilcek J., Sehgal P. B. Induction of beta 2-interferon by tumor necrosis factor: a homeostatic mechanism in the control of cell proliferation. Cell. 1986 Jun 6;45(5):659–666. doi: 10.1016/0092-8674(86)90780-4. [DOI] [PubMed] [Google Scholar]
  17. Kvale D., Løvhaug D., Sollid L. M., Brandtzaeg P. Tumor necrosis factor-alpha up-regulates expression of secretory component, the epithelial receptor for polymeric Ig. J Immunol. 1988 May 1;140(9):3086–3089. [PubMed] [Google Scholar]
  18. Le J. M., Vilcek J. Interleukin 6: a multifunctional cytokine regulating immune reactions and the acute phase protein response. Lab Invest. 1989 Dec;61(6):588–602. [PubMed] [Google Scholar]
  19. Le J., Vilcek J. Tumor necrosis factor and interleukin 1: cytokines with multiple overlapping biological activities. Lab Invest. 1987 Mar;56(3):234–248. [PubMed] [Google Scholar]
  20. Leist T. P., Frei K., Kam-Hansen S., Zinkernagel R. M., Fontana A. Tumor necrosis factor alpha in cerebrospinal fluid during bacterial, but not viral, meningitis. Evaluation in murine model infections and in patients. J Exp Med. 1988 May 1;167(5):1743–1748. doi: 10.1084/jem.167.5.1743. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Levi S., Beardshall K., Haddad G., Playford R., Ghosh P., Calam J. Campylobacter pylori and duodenal ulcers: the gastrin link. Lancet. 1989 May 27;1(8648):1167–1168. doi: 10.1016/s0140-6736(89)92752-9. [DOI] [PubMed] [Google Scholar]
  22. Lewis C. E., McCarthy S. P., Lorenzen J., McGee J. O. Differential effects of LPS, IFN-gamma and TNF alpha on the secretion of lysozyme by individual human mononuclear phagocytes: relationship to cell maturity. Immunology. 1990 Mar;69(3):402–408. [PMC free article] [PubMed] [Google Scholar]
  23. Linder H., Engberg I., van Kooten C., de Man P., Svanborg-Edén C. Effects of anti-inflammatory agents on mucosal inflammation induced by infection with gram-negative bacteria. Infect Immun. 1990 Jul;58(7):2056–2060. doi: 10.1128/iai.58.7.2056-2060.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Marshall B. J., Warren J. R. Unidentified curved bacilli in the stomach of patients with gastritis and peptic ulceration. Lancet. 1984 Jun 16;1(8390):1311–1315. doi: 10.1016/s0140-6736(84)91816-6. [DOI] [PubMed] [Google Scholar]
  25. Nelson S., Bagby G. J., Bainton B. G., Wilson L. A., Thompson J. J., Summer W. R. Compartmentalization of intraalveolar and systemic lipopolysaccharide-induced tumor necrosis factor and the pulmonary inflammatory response. J Infect Dis. 1989 Feb;159(2):189–194. doi: 10.1093/infdis/159.2.189. [DOI] [PubMed] [Google Scholar]
  26. Papadimitriou C. S., Ioachim-Velogianni E. E., Tsianos E. B., Moutsopoulos H. M. Epithelial HLA-DR expression and lymphocyte subsets in gastric mucosa in type B chronic gastritis. Virchows Arch A Pathol Anat Histopathol. 1988;413(3):197–204. doi: 10.1007/BF00718611. [DOI] [PubMed] [Google Scholar]
  27. Parsonnet J., Gillis Z. A. Production of tumor necrosis factor by human monocytes in response to toxic-shock-syndrome toxin-1. J Infect Dis. 1988 Nov;158(5):1026–1033. doi: 10.1093/infdis/158.5.1026. [DOI] [PubMed] [Google Scholar]
  28. Peterson G. L. A simplification of the protein assay method of Lowry et al. which is more generally applicable. Anal Biochem. 1977 Dec;83(2):346–356. doi: 10.1016/0003-2697(77)90043-4. [DOI] [PubMed] [Google Scholar]
  29. Rathbone B. J., Wyatt J. I., Heatley R. V. Campylobacter pyloridis--a new factor in peptic ulcer disease? Gut. 1986 Jun;27(6):635–641. doi: 10.1136/gut.27.6.635. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Rathbone B. J., Wyatt J. I., Worsley B. W., Shires S. E., Trejdosiewicz L. K., Heatley R. V., Losowsky M. S. Systemic and local antibody responses to gastric Campylobacter pyloridis in non-ulcer dyspepsia. Gut. 1986 Jun;27(6):642–647. doi: 10.1136/gut.27.6.642. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Rook G. A., Taverne J., Leveton C., Steele J. The role of gamma-interferon, vitamin D3 metabolites and tumour necrosis factor in the pathogenesis of tuberculosis. Immunology. 1987 Oct;62(2):229–234. [PMC free article] [PubMed] [Google Scholar]
  32. Slagle D. C., Cox R. A., Kuruganti U. Induction of tumor necrosis factor alpha by spherules of Coccidioides immitis. Infect Immun. 1989 Jul;57(7):1916–1921. doi: 10.1128/iai.57.7.1916-1921.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Steinbeck M. J., Roth J. A. Neutrophil activation by recombinant cytokines. Rev Infect Dis. 1989 Jul-Aug;11(4):549–568. doi: 10.1093/clinids/11.4.549. [DOI] [PubMed] [Google Scholar]
  34. Strieter R. M., Kunkel S. L., Showell H. J., Marks R. M. Monokine-induced gene expression of a human endothelial cell-derived neutrophil chemotactic factor. Biochem Biophys Res Commun. 1988 Nov 15;156(3):1340–1345. doi: 10.1016/s0006-291x(88)80779-4. [DOI] [PubMed] [Google Scholar]
  35. Strieter R. M., Phan S. H., Showell H. J., Remick D. G., Lynch J. P., Genord M., Raiford C., Eskandari M., Marks R. M., Kunkel S. L. Monokine-induced neutrophil chemotactic factor gene expression in human fibroblasts. J Biol Chem. 1989 Jun 25;264(18):10621–10626. [PubMed] [Google Scholar]
  36. Uehara A., Okumura T., Sekiya C., Okamura K., Takasugi Y., Namiki M. Interleukin-1 inhibits the secretion of gastric acid in rats: possible involvement of prostaglandin. Biochem Biophys Res Commun. 1989 Aug 15;162(3):1578–1584. doi: 10.1016/0006-291x(89)90855-3. [DOI] [PubMed] [Google Scholar]
  37. Valnes K., Brandtzaeg P., Elgjo K., Stave R. Specific and nonspecific humoral defense factors in the epithelium of normal and inflamed gastric mucosa. Immunohistochemical localization of immunoglobulins, secretory component, lysozyme, and lactoferrin. Gastroenterology. 1984 Mar;86(3):402–412. [PubMed] [Google Scholar]
  38. Waage A., Halstensen A., Espevik T. Association between tumour necrosis factor in serum and fatal outcome in patients with meningococcal disease. Lancet. 1987 Feb 14;1(8529):355–357. doi: 10.1016/s0140-6736(87)91728-4. [DOI] [PubMed] [Google Scholar]
  39. Whitehead R., Truelove S. C., Gear M. W. The histological diagnosis of chronic gastritis in fibreoptic gastroscope biopsy specimens. J Clin Pathol. 1972 Jan;25(1):1–11. doi: 10.1136/jcp.25.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Wyatt J. I., Dixon M. F. Chronic gastritis--a pathogenetic approach. J Pathol. 1988 Feb;154(2):113–124. doi: 10.1002/path.1711540203. [DOI] [PubMed] [Google Scholar]
  41. de Man P., van Kooten C., Aarden L., Engberg I., Linder H., Svanborg Edén C. Interleukin-6 induced at mucosal surfaces by gram-negative bacterial infection. Infect Immun. 1989 Nov;57(11):3383–3388. doi: 10.1128/iai.57.11.3383-3388.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Gut are provided here courtesy of BMJ Publishing Group

RESOURCES