Elevated gaseous luminal nitric oxide and circulating IL-8 as features of Helicobacter pylori-induced gastric inflammation

  • Hiwa K. Saaed Department of Medical Sciences, Gastroenterology and Hepatology Unit, Uppsala University, Uppsala, Sweden https://orcid.org/0000-0003-1078-514X
  • Lisa Chiggiato Department of Medical Sciences, Gastroenterology and Hepatology Unit, Uppsala University, Uppsala, Sweden https://orcid.org/0000-0003-2784-8880
  • Dominic-Luc Webb Department of Medical Sciences, Gastroenterology and Hepatology Unit, Uppsala University, Uppsala, Sweden https://orcid.org/0000-0002-6979-9194
  • Ann-Sofie Rehnberg Department of Gastroenterology and Hepatology, Karolinska University Hospital Solna, Karolinska Institute, Stockholm, Sweden
  • Carlos A. Rubio Department of Pathology, Karolinska University Hospital Solna, Karolinska Institute, Stockholm, Sweden https://orcid.org/0000-0003-3879-5729
  • Ragnar Befrits Department of Gastroenterology and Hepatology, Karolinska University Hospital Solna, Karolinska Institute, Stockholm, Sweden
  • Per M. Hellström Department of Medical Sciences, Gastroenterology and Hepatology Unit, Uppsala University, Uppsala, Sweden https://orcid.org/0000-0001-8428-0772
Keywords: Nitric oxide, Helicobacter pylori, inflammation, cytokines, biomarkers


Background: Gastric nitric oxide (NO) production in response to Helicobacter pylori via inducible nitric oxide synthase (iNOS) is suggested as a biomarker of inflammation and cytotoxicity. The aim of this study was to investigate relationships between gastric [NO], immunological biomarkers and histopathology.

Materials and methods: Esophagogastroduodenoscopy was done in 96 dyspepsia patients. Luminal [NO] was measured by chemiluminescence. Biopsies were taken from gastric antrum and corpus for culture and histopathology. H. pylori IgG was detected by immunoblot assay. Biobanked plasma from 76 dyspepsia patients (11 H. pylori positives) was analyzed for 39 cytokines by multiplexed ELISA.

ResultsH. pylori-positive patients had higher [NO] (336 ± 26 ppb, mean ± 95% CI, n = 77) than H. pylori-negative patients (128 ± 47 ppb, n = 19) (P < 0.0001). Histopathological changes were found in 99% of H. pylori-positive and 37% of H. pylori-negative patients. Histopathological concordance was 78–100% between corpus and antrum. Correlations were found between gastric [NO] and severity of acute, but not chronic, inflammation. Plasma IL-8 (increased in H. pylori positives) had greatest difference between positive and negative groups, with eotaxin, MIP-1β, MCP-4, VEGF-A, and VEGF-C also higher (P < 0.004 to P < 0.032). Diagnostic odds ratios using 75% cut-off concentration were 7.53 for IL-8, 1.15 for CRP, and 2.88 for gastric NO.

Conclusions: Of the parameters tested, increased gastric [NO] and circulating IL-8 align most consistently and selectively in H. pylori-infected patients. Severity of mucosal inflammatory changes is proportional to luminal [NO], which might be tied to IL-8 production. It is proposed that IL-8 be further investigated as a blood biomarker of treatment outcomes.


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How to Cite
Saaed, H. K., Chiggiato, L., Webb, D.-L., Rehnberg, A.-S., Rubio, C. A., Befrits, R., & Hellström, P. M. (2021). Elevated gaseous luminal nitric oxide and circulating IL-8 as features of <em>Helicobacter pylori</em&gt;-induced gastric inflammation. Upsala Journal of Medical Sciences, 126(1). https://doi.org/10.48101/ujms.v126.8116
Original Articles