P>Background Chronic allergic asthma is the result of a T-helper type 2 (Th2)-biased immune status. Current asthma therapies control symptoms in some patients, but a long-lasting therapy has not been established. Anti-Asthma Simplified Herbal Medicine Intervention (ASHMI (TM)), a Chinese herbal formula improved symptoms and lung function, and reduced Th2 responses in a controlled trial of patients with persistent moderate to severe asthma. Objective We evaluated the persistence of ASHMI (TM) beneficial effects following therapy in a murine model of chronic asthma and the immunological mechanisms underlying such effects. Methods BALB/c mice sensitized intraperitoneally with ovalbumin (OVA) received 3 weekly intratracheal OVA challenges to induce airway hyper-reactivity (AHR) and inflammation (OVA mice). Additionally, OVA mice were treated with ASHMI (TM) (OVA/ASHMI (TM)) or water (OVA/sham) for 4 weeks, and then challenged immediately and 8 weeks post-therapy. In other experiments, OVA mice received ASHMI (TM) treatment with concomitant neutralization of IFN-gamma or TGF-beta. Effects on airway responses, cytokine- and OVA-specific IgE levels were determined 8 weeks post-therapy. Results Before treatment, OVA mice exhibited AHR and pulmonary eosinophilic inflammation following OVA challenge, which was almost completely resolved immediately after completing treatment with ASHMI (TM) and did not re-occur following OVA re-challenge up to 8 weeks post-therapy. Decreased allergen-specific IgE and Th2 cytokine levels, and increased IFN-gamma levels also persisted at least 8 weeks post-therapy. ASHMI (TM) effects were eliminated by the neutralization of IFN-gamma, but not TGF-beta, during therapy. Conclusion ASHMI (TM) induced long-lasting post-therapy tolerance to antigen-induced inflammation and AHR. IFN-gamma is a critical factor in ASHMI (TM) effects. Cite this as: K. Srivastava, T. Zhang, N. Yang, H. Sampson and X. M. Li, Clinical & Experimental Allergy, 2010 (40) 1678-1688.
