Antibiotic use during infancy promotes a shift in the T_H1/T_H2 balance toward T_H2-dominant immunity in mice

Background: Recent epidemiologic studies indicate that antibiotic use in infancy may be associated with an increased risk of development of atopy; however, its precise mechanism remains to be elucidated. Objective: The purpose of this study is to clarify whether one such antibiotic, kanamycin, affects the T_H1/T_H2 balance. Methods: BALB/c mice at 3 and 52 weeks of age were orally administered 600 mg/d kanamycin sulfate for 7 consecutive days. Blood samples were collected on weeks 0, 10, 18, and 26 after the cessation of kanamycin treatment, and the effect of the kanamycin treatment on the T_H1/T_H2 balance was evaluated on the basis of both the in vivo antibody levels and the in vitro splenocyte cytokine secretion pattern. Results: The administration of kanamycin increased the serum levels of total IgG1 and IgE while decreasing the serum IgG2a levels. Moreover, when spleen cells were stimulated with immobilized anti-CD3 antibody in vitro, such kanamycin treatment enhanced the in vitro IL-4 secretion while reducing the in vitro IFN-γ secretion. The basal IL-12 p70 secretion levels of splenic dendritic cells in the kanamycin-treated mice were lower than those in the control mice, although no significant difference was seen in IL-12 p40 levels between either group of mice. Conclusion: These results suggested that antibiotic use during infancy may indeed quantitatively disturb, qualitatively disturb, or both the intestinal microflora and thereby prevent postnatal T_H1 cell maturation, thus resulting in a T_H2-polarized immune deviation.