Helicobacter pylori infection in interleukin-4-deficient and transgenic mice

Interleukin (IL)-4 is a potent anti-inflammatory and Th2-type immunoregulatory cytokine. Helicobacter pylori infection in humans induces a polarized Th1 immune response characterized by increased production of interferon-gamma and absence of IL-4. This study was designed to determine the role of endogenous IL-4 in the host defence against gastric colonization by H. pylori using IL-4-deficient (IL-4-/-) and transgenic (IL-4 Tg) mice.

IL-4-/- mice and IL-4 Tg mice were inoculated intragastrically with H. pylori Sydney Strain 1. Gastric colonization by H. pylori (biopsy urease test and bacterial colony counts), serum levels of H. pylori-specific immunoglobulin M, A, G, isotypes of IgG, and the gastric mucosal inflammatory scores were determined 6 weeks after inoculation. Results were compared with those obtained from H. pylori-infected IL-4+/+ (controls for IL-4-/- mice) and IL-4 WT (controls for IL-4 Tg) mice.

Colonization of the gastric mucosa by H. pylori in IL-4-/- mice was similar to that of control IL-4+/+ mice. There was no significant difference in titres of H. pylori-specific antibodies or gastric inflammatory scores between the two groups of mice. Colonization of gastric mucosa by H. pylori was consistently lower in IL-4 Tg mice (log10 6.40+/-1.09 CFU/g tissue) compared with IL-4WT mice (log10 7.20+/-0.34 CFU/g tissue), although the difference was not significant. Nevertheless, IL-4 Tg mice did have significantly higher titres of H. pylori-specific IgA and IgG (P< or =0.01).

These results show that endogenous IL-4 is not a major contributor to host resistance to H. pylori, and enhanced IL-4 production has little if any effect on gastric colonization by this organism, despite increased specific antibody production.