Background: A unique pathological feature of murine autoimmune gastritis (AIG) is its pronounced mucosal hypertrophy, which is different from human type A chronic atrophic gastritis with pernicious anemia. The aim of this study was to clarify the mechanism of gastric hypertrophy in murine AIG, especially in relation to inflammatory cells infiltrating the gastric mucosa.
Methods: Neonatally thymectomized (NTx) BALB/c and (BALB/c x DBA/2) F1 mice with gastritis were examined histologically and serologically. The T-helper (Th1/Th2) immune balance in the spleen was evaluated by intracellular cytokine staining for interferon-gamma and a flow-cytometric beads array for several cytokines. Additionally, NTx AIG BALB/c mice were orally administered an H(2)-blocker to decrease eosinophils.
Results: NTx AIG BALB/c mice exhibited gastritis without stomach hypertrophy at 2 months of age, and developed gastritis with mucous gland hypertrophy accompanied by eosinophil infiltration at 6 months of age. In contrast, NTx AIG (BALB/c x DBA/2) F1 mice displayed gastritis with neither stomach hypertrophy nor eosinophil infiltration even at the age of 6 months. Upregulation of interleukin-4 and granulocyte-macrophage colony-stimulating factor in the spleen was observed in BALB/c mice but not in (BALB/c x DBA/2) F1 mice. Additionally, some NTx AIG BALB/c mice did not show gastric hypertrophy or eosinophil infiltration owing to the administration of an H(2)-blocker.
Conclusions: There are two different pathological phenotypes of murine AIG, chronic gastritis and hypertrophic gastritis, in NTx AIG BALB/c mice. Furthermore, eosinophil infiltration and the Th2 immune response might play a key role in the phenotypic shift from chronic gastritis to hypertrophic gastritis in these mice.