Abstract
BackgroundGastric 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 methodsEsophagogastroduodenoscopy 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.ConclusionsOf 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.
Highlights
A troubling feature of Helicobacter pylori (H. pylori) is its persistence within the stomach via a combination of host, environmental, and bacterial factors [1, 2]
Further investigations are needed to build concensus on human in vivo pathophysiology in H. pylori infection as to whether nitric oxide (NO) is detectable in the gastric lumen, whether detected NO is traceable to inducible nitric oxide synthase (iNOS), which circulating cytokines are most likely tied to NO and H. pylori under different conditions, and how cytokines relate to C-reactive protein (CRP)
Many researchers have assumed increased NO elaboration based on the expression of different NOS isoforms [14, 15]
Summary
A troubling feature of Helicobacter pylori (H. pylori) is its persistence within the stomach via a combination of host, environmental, and bacterial factors [1, 2]. Gene and protein expressions of inducible nitric oxide (NO) synthase (iNOS, a product of NOS2 gene) are increased in gastric tissue in H. pylori infection [5]. Previous studies exploring cytokine panels of blood protein and tissue RNA concentration demonstrated the production of many immune signaling molecules in H. pylori infection [6, 7], albeit with somewhat different outcomes. Further investigations are needed to build concensus on human in vivo pathophysiology in H. pylori infection as to whether NO is detectable in the gastric lumen, whether detected NO is traceable to iNOS, which circulating cytokines are most likely tied to NO and H. pylori under different conditions (e.g. acute vs chronic inflammation), and how cytokines relate to CRP. It is proposed that IL-8 be further investigated as a blood biomarker of treatment outcomes
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