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

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 histo...

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Main Authors: Hiwa K. Saaed, Lisa Chiggiato, Dominic-Luc Webb, Ann-Sofie Rehnberg, Carlos A. Rubio, Ragnar Befrits, Per M. Hellström
Format: Article
Language:English
Published: Upsala Medical Society 2021-10-01
Series:Upsala Journal of Medical Sciences
Subjects:
Online Access:https://ujms.net/index.php/ujms/article/view/8116/13987
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author Hiwa K. Saaed
Lisa Chiggiato
Dominic-Luc Webb
Ann-Sofie Rehnberg
Carlos A. Rubio
Ragnar Befrits
Per M. Hellström
author_facet Hiwa K. Saaed
Lisa Chiggiato
Dominic-Luc Webb
Ann-Sofie Rehnberg
Carlos A. Rubio
Ragnar Befrits
Per M. Hellström
author_sort Hiwa K. Saaed
collection DOAJ
description 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. Results: H. 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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spelling doaj.art-69c340234e45456ba22a6df66e9f23632023-09-02T16:56:44ZengUpsala Medical SocietyUpsala Journal of Medical Sciences0300-97342000-19672021-10-011261910.48101/ujms.v126.81168116Elevated gaseous luminal nitric oxide and circulating IL-8 as features of Helicobacter pylori-induced gastric inflammationHiwa K. Saaed0Lisa Chiggiato1Dominic-Luc Webb2Ann-Sofie Rehnberg3Carlos A. Rubio4Ragnar Befrits5Per M. Hellström6Department of Medical Sciences, Gastroenterology and Hepatology Unit, Uppsala University, Uppsala, SwedenDepartment of Medical Sciences, Gastroenterology and Hepatology Unit, Uppsala University, Uppsala, SwedenDepartment of Medical Sciences, Gastroenterology and Hepatology Unit, Uppsala University, Uppsala, SwedenDepartment of Gastroenterology and Hepatology, Karolinska University Hospital Solna, Karolinska Institute, Stockholm, SwedenDepartment of Pathology, Karolinska University Hospital Solna, Karolinska Institute, Stockholm, SwedenDepartment of Gastroenterology and Hepatology, Karolinska University Hospital Solna, Karolinska Institute, Stockholm, SwedenDepartment of Medical Sciences, Gastroenterology and Hepatology Unit, Uppsala University, Uppsala, SwedenBackground: 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. Results: H. 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.https://ujms.net/index.php/ujms/article/view/8116/13987nitric oxidehelicobacter pyloriinflammationcytokinesbiomarkers
spellingShingle Hiwa K. Saaed
Lisa Chiggiato
Dominic-Luc Webb
Ann-Sofie Rehnberg
Carlos A. Rubio
Ragnar Befrits
Per M. Hellström
Elevated gaseous luminal nitric oxide and circulating IL-8 as features of Helicobacter pylori-induced gastric inflammation
Upsala Journal of Medical Sciences
nitric oxide
helicobacter pylori
inflammation
cytokines
biomarkers
title Elevated gaseous luminal nitric oxide and circulating IL-8 as features of Helicobacter pylori-induced gastric inflammation
title_full Elevated gaseous luminal nitric oxide and circulating IL-8 as features of Helicobacter pylori-induced gastric inflammation
title_fullStr Elevated gaseous luminal nitric oxide and circulating IL-8 as features of Helicobacter pylori-induced gastric inflammation
title_full_unstemmed Elevated gaseous luminal nitric oxide and circulating IL-8 as features of Helicobacter pylori-induced gastric inflammation
title_short Elevated gaseous luminal nitric oxide and circulating IL-8 as features of Helicobacter pylori-induced gastric inflammation
title_sort elevated gaseous luminal nitric oxide and circulating il 8 as features of helicobacter pylori induced gastric inflammation
topic nitric oxide
helicobacter pylori
inflammation
cytokines
biomarkers
url https://ujms.net/index.php/ujms/article/view/8116/13987
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