Increased Gastric IL-1β Concentration and Iron Deficiency Parameters in H. pylori Infected Children

Abstract

Association between H. pylori infection, iron deficiency and iron deficiency anaemia has been described, but the mechanisms involved have not been established. We hypothesized that in H. pylori infected children increased gastric concentrations of IL-1β and/or TNF-α, both potent inhibitors of gastric acid secretion that is essential for iron absorption, are predictors for low blood concentrations of ferritin and haemoglobin, markers of early depletion of iron stores and anaemia, respectively. We evaluated 125 children undergoing endoscopy to clarify the origin of gastrointestinal symptoms. Gastric specimens were obtained for H. pylori status and cytokine evaluation and blood samples for determination of iron deficiency/iron deficiency anaemia parameters and IL1 cluster and TNFA polymorphisms that are associated with increased cytokine secretions. Higher IL-1β and TNF-α gastric concentrations were observed in H. pylori-positive (n = 47) than in -negative (n = 78) children. Multiple linear regression models revealed gastric IL-1β, but not TNF-α, as a significant predictor of low ferritin and haemoglobin concentrations; results were reproduced in young children in whom IL1RN polymorphic genotypes associated with higher gastric IL-1β expression and lower blood ferritin and haemoglobin concentrations. In conclusion, high gastric levels of IL-1β can be the link between H. pylori infection and iron deficiency/iron deficiency anaemia in childhood.

Iron Status and Helicobacter pylori Infection in Symptomatic Children: An International Multi-Centered Study

“…Furthermore, in the H. pylori -positive Chilean children, an association between low serum iron and transferrin and hypochlorhydria was observed [27]. Of note, in the Brazilian cohort, the concentration of gastric IL-1β, a potent inhibitor of gastric acid secretion, was inversely associated with blood ferritin and haemoglobin concentrations [28]. Consistent with these results, significant negative associations were also observed between the infection and other iron deficiency parameters: haematocrit, MCV and MCH.…”

High Resolution Electron Microscopy of the <em>Helicobacter pylori</em> Cag Type IV Secretion System Pili Produced in Varying Conditions of Iron Availability

“…These facts support the hypothesis that reduced iron availability increases the production of Cag-T4SS pili at the host pathogen interface resulting in worse gastric disease [11][12][13][14] . The goal of the method provided in this manuscript is to establish the role of the micronutrient iron in the regulation of the Cag-T4SS pilus biogenesis.…”

“…However, disease outcomes vary and depend on numerous factors such as host genetics, genetic diversity of H. pylori strains, and environmental elements such as host diet 11 . Previous reports have established that a correlation exists between H. pylori infection, iron deficiency (as measured by decreased blood ferritin and hemoglobin concentrations), and increased proinflammatory cytokine production, including IL-8 secretion, which ultimately leads to increased gastric disease progression 12 . Acute H. pylori infection is also associated with hypochlorhydria which impairs the host's ability to absorb nutrient iron, and ultimately leads to changes in iron homeostasis 13 .…”

Association of the IL-1RN variable number of tandem repeat polymorphism and Helicobacter pylori infection: A meta-analysis

“…A study by Queiroz et al . [39] was found to be the source of heterogeneity by omitting each study in turn. When sensitivity analyses were conducted, the pooled ORs were not significantly altered.…”