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Relationship between mucosal levels of interleukin 8 and toxinogenicity of Helicobacter pylori

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Abstract

Aim of study: To investigate if an association exists between in-vivo mucosal levels of IL-8 and bacterial expression of cytotoxin and cagA gene of H. pylori.

Methods: Seventy-two dyspeptic patients referred for endoscopy were studied, including 36 patients with peptic ulcer (PU) and 36 with non-ulcer dyspepsia (NUD). Biopsies were taken for histology, H. pylori culture and measurement of IL-8 by ELISA. To test the ability of H. pylori to produce cytotoxin (VacA), broth culture supernatants were assayed on Vero cells and vacuolation measured. PCR was used to detect the cagA gene of H. pylori.

Results: H. pylori was isolated in 52 of 72 patients studied. Among the 52 strains, 25 (49%) were VacA+ve/cagA+ve; 12 (23%) were VacA−ve/cagA−ve; the remaining 15 strains (28%) were either VacA+ve/cagA−ve or VacA−ve/cagA+ve. IL-8 levels (median (interquartile) pg/mg) in patients infected with VacA+ve (1.5 (0.64, 2.84)) or cagA+ve strains (1.25 (0.72, 2.34) were significantly higher than in those with VacA−ve (0.76 (0.4, 1.0)) or cagA−ve strains (0.5 (0.4, 1.5); p<0.05). The neutrophil infiltration score was also higher in patients infected with VacA+ve or cagA+ve strains than in those infected with VacA−ve or cagA−ve strains (p<0.05).

Conclusion: VacA+ve/cagA+ve strains were associated with an enhanced production of mucosal IL-8 in vivo and correlated with a stronger infiltration of neutrophils. Enhanced mucosal production of IL-8 and its role in neutrophil chemotaxis and activation could be important in H. pylori-induced gastroduodenal inflammation and in the development of peptic ulcer disease.

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References

  1. Marshall BJ, Warren JR. Unidentified curved bacilli in the stomach of patients with gastritis and peptic ulceration. Lancet. 1984;1:1311–15.

    Article  PubMed  CAS  Google Scholar 

  2. Rauws EAJ, Tytgat GNT. Eradication of Helicobacter pylori cures duodenal ulcer. Lancet. 1990;335:1233–5.

    Article  PubMed  CAS  Google Scholar 

  3. Morris A, Nicholson G. Ingestion of Campylobacter pyloridis causes gastritis and raised fasting gastric pH. Am J Gastroenterol. 1987;82:192–9.

    PubMed  CAS  Google Scholar 

  4. Moss S, Calam J. Helicobacter pylori and peptic ulcers: the present position. Gut. 1992;33:289–92.

    PubMed  CAS  Google Scholar 

  5. Blaser MJ. Hypothesis on the pathogenesis and natural history of Helicobacter pylori-induced inflammation. Gastroenterology. 1992;102:720–7.

    PubMed  CAS  Google Scholar 

  6. Blaser MJ, Parsonnet J. Parasitism by the ‘slow’ bacterium Helicobacter pylori leads to altered gastric homeostasis and neoplasia. J Clin Invest. 1994;94:4–8.

    PubMed  CAS  Google Scholar 

  7. Newell D. The pathogenic mechanism of Helicobacter pylori — a comment. In: Malfertheiner P, Ditschuneit H, eds. Helicobacter pylori, Gastritis and Peptic Ulcer. Berlin: Springer; 1990:128–33.

    Google Scholar 

  8. Figura N, Gutlielmetti P, Rossolinia A et al. Cytotoxin production by Campylobacter pylori strains isolated from patients with peptic ulcers and from patients with chronic gastritis only. J Clin Microbiol. 1989;27:225–6.

    PubMed  CAS  Google Scholar 

  9. Leunk RD, Johnson PT, David BC, Kraft WG, Morgan DR. Cytotoxic activity in broth-culture filtrates of Campylobacter pylori. J Med Microbiol. 1988;26:93–9.

    Article  PubMed  CAS  Google Scholar 

  10. Goossens H, Glupczynski Y, Burette A et al. Role of the vacuolating toxin from Helicobacter pylori in the pathogenesis of duodenal and gastric ulcer. Med Microbiol Lett. 1992;1:153–9.

    Google Scholar 

  11. Atherton JC, Peek RM Jr, Tham KT, Cover TL, Blaser MJ. Clinical and pathological importance of heterogeneity in VacA, the vacuolating cytotoxin gene of Helicobacter pylori. Gastroenterology. 1997;112:92–9.

    Article  PubMed  CAS  Google Scholar 

  12. Crabtree JE, Taylor JD, Wyatt JL et al. Mucosal IgA recognition of Helicobacter pylori 120 kDa protein, peptic ulceration, and gastric pathology. Lancet. 1991;338:332–5.

    Article  PubMed  CAS  Google Scholar 

  13. Cover TL, Blaser MJ. Helicobacter pylori and gastroduodenal disease. Annu Rev Med. 1992;43:135–45.

    Article  PubMed  CAS  Google Scholar 

  14. Davies GR, Banatvala N, Collins CE et al. Relationship between infective load of Helicobacter pylori and reactive oxygen metabolite production in antral mucosa. Scand J Gastroenterol. 1994;29:419–24.

    PubMed  CAS  Google Scholar 

  15. Graham DY. Pathogenic mechanisms leading to Helicobacter pylori induced inflammation. Eur J Gastroenterol Hepatol. 1991;4S:9–16.

    Google Scholar 

  16. Baggiolini M, Walz A, Kunkel SL. Neutrophil-activating peptide-1/interleukin 8, a novel cytokine that activates neutrophils. J Clin Invest. 1989;84:1045–9.

    Article  PubMed  CAS  Google Scholar 

  17. Crabtree JE, Lindley IJD. Mucosal interleukin-8 and Helicobacter pylori-associated gastroduodenal disease. Eur J Gastroenterol Hepatol. 1994;6(Suppl. 1):S33–8.

    PubMed  Google Scholar 

  18. Fan XG, Chua A, Fan XJ, Keeling PMN. Increased gastric production of interleukin-8 and tumour necrosis factor in Helicobacter pylori infection. J Clin Pathol. 1995;48:133–6.

    Article  PubMed  CAS  Google Scholar 

  19. Crabtree JE, Peichl P, Wyatt JI, Stachl U, Lindley IJD. Gastric IL-8 and IL-8 IgA autoantibodies in Helicobacter pylori infection. Scand J Immunol. 1993;37:65–70.

    Article  PubMed  CAS  Google Scholar 

  20. Crabtree JE, Farmery SM, Lindley IJD, Figura N, Peichl P, Tompkins DS. CagA/cytotoxic status of Helicobacter pylori and interleukin-8 in gastric epithelial cell lines. J Clin Pathol. 1994;47:945–50.

    Article  PubMed  CAS  Google Scholar 

  21. Crabtree JE, Covacci A, Farmery SM et al. Helicobacter pylori-induced interleukin 8 expression in gastric epithelial cells is associated with CagA positive phenotype. J Clin Pathol. 1995;48:41–5.

    Article  PubMed  CAS  Google Scholar 

  22. Crabtree JE, Xiang Z, Lindley IJD et al. Induction of interleukin-8 secretion from gastric epithelial cells by cagA negative isogenic mutant of Helicobacter pylori. J Clin Pathol. 1995;48:967–9.

    Article  PubMed  CAS  Google Scholar 

  23. Sharma SA, Tummuru MKR, Miller GG, Blaser MJ. Interleukin-8 response of gastric epithelial cell lines to Helicobacter pylori stimulation in vitro. Infect Immun. 1995;63:1681–7.

    PubMed  CAS  Google Scholar 

  24. Huang JZ, O’Toole PW, Doig P, Trust TJ. Stimulation of interleukin-8 production in epithelial cell lines by Helicobacter pylori. Infect Immun. 1995;63:1732–8.

    PubMed  CAS  Google Scholar 

  25. Zhang QB, Dawodu JB, Husain A, Etolhi G, Gemmell CG, Russell RI. Association of antral mucosal levels of interleukin 8 and reactive oxygen radicals in patients with Helicobacter pylori. Clin Sci. 1997;92:69–73.

    PubMed  CAS  Google Scholar 

  26. Zhang QB, Nakshabendi IM, Mokhashi MS, Dawodu JB, Gemmell CG, Russell RI. Association of cytotoxin production and neutrophil activation by strains of Helicobacter pylori isolated from patients with peptic ulceration and chronic gastritis. Gut. 1996;38:841–5.

    PubMed  CAS  Google Scholar 

  27. Cover TL, Puryear W, Perez-Perez GI, Blaser MJ. Effect of urease on HaLa cell vacuolation induced by Helicobacter pylori cytotoxin. Infect Immun. 1991;59:1264–70.

    PubMed  CAS  Google Scholar 

  28. Ende AVD, Rauws EAJ, Feller M, Mulder CJJ, Tytgat GNJ, Dankert J. Heterogeneous Helicobacter pylori isolates from members of a family with a history of peptic ulcer disease. Gastroenterology. 1996;111:638–647.

    Article  PubMed  Google Scholar 

  29. Covacci A, Censini S, Bugnoli M et al. Molecular characterization of the 128-kDa immunodominant antigen of Helicobacter pylori associated with cytotoxicity and duodenal ulcer. Proc Natl Acad Sci USA. 1993;90:5791–5.

    Article  PubMed  CAS  Google Scholar 

  30. Peek RM, Miller GG, Tham KT et al. Heightened inflammatory response and cytokine expression in vivo to cagA+ Helicobacter pylori strains. Lab Invest. 1995;73:760–70.

    PubMed  CAS  Google Scholar 

  31. Censini S, Lange C, Xiang Z et al. cag, a pathogenicity island of Helicobacter pylori, encodes type I-specific and disease-associated virulence factors. Proc Natl Acad Sci USA. 1996;93:14648–53.

    Article  PubMed  CAS  Google Scholar 

  32. Xiang Z, Censini S, Bayeli PF et al. Analysis of expression of CagA and VacA virulence factors in 43 strains of Helicobacter pylori reveals that clinical isolates can be divided into two major types and that CagA is not necessary for expression of the vacuolating cytotoxin. Infect Immun. 1995;63:94–8.

    PubMed  CAS  Google Scholar 

  33. Atherton JC, Cao P, Peek RM Jr, Tummuru MKR, Blaser MJ, Cover TL. Mosaicism in vacuolating cytotoxin alleles of Helicobacter pylori: association of specific vacA types with cytotoxin production and peptic ulceration. J Biol Chem. 1995;270:17771–7.

    Article  PubMed  CAS  Google Scholar 

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Zhang, Q.B., Etolhi, G., Dawodu, J.B. et al. Relationship between mucosal levels of interleukin 8 and toxinogenicity of Helicobacter pylori . Inflammopharmacol 6, 109–117 (1998). https://doi.org/10.1007/s10787-998-0028-y

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  • DOI: https://doi.org/10.1007/s10787-998-0028-y

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