Impaired host immunity contributes to Helicobacter pylori eradication failure

Effective eradication of Helicobacter pylori (H. pylori) infection has often proved more difficult than expected. Antimicrobial resistance incompletely explains eradication failure. This study tests the hypothesis that an impaired immune response may contribute to failed eradication after standard antibiotic therapy.

Parameters of host immunity were assessed as blood T lymphocyte production of interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) being surrogate markers of mucosal Th1 and Th2 responses, respectively. The validity of using circulating T cell cytokines as surrogate markers of mucosal immunity was established (unstimulated lymphocyte IL-4 level correlation r2 = 0.549, p < 0.001; antigen-stimulated lymphocyte correlation r2 = 0.62, p < 0.001).

A total of 52 dyspeptic patients and 11 patients with previous H. pylori eradication failure were recruited into the study. There was no significant difference in secretion of IFN-gamma from peripheral blood T cells, in either unstimulated or antigen-stimulated cultures, between clinical groups. There was, however, a significant reduction in secretion of IL-4 from blood T cells in subjects failing to eradicate H. pylori compared with those who successfully eradicated the infection in both unstimulated and stimulated cultures. A significant difference in IL-4 secretion was also detected in antigen-stimulated cultures compared with that in H. pylori-positive subjects (p < 0.05). Low levels of IL-4 secretion were detected irrespective of the number of courses of antibiotic therapy. Lower levels of IgG anti-H. pylori antibody were detected in both serum and saliva of subjects with persistent H. pylori infection after use of antibiotics compared with untreated H. pylori-positive subjects (difference not statistically significant).

These results support the hypothesis that impaired mucosal immunity, particularly involving the secretion of IL-4, may contribute to H. pylori eradication failure. Measurement of whole blood secretion of IL-4 may predict which patients are more likely to fail standard antibiotic therapy.