title: Anti-Asthma Simplified Herbal Medicine Intervention-induced long-lasting tolerance to allergen exposure in an asthma model is interferon-γ, but not transforming growth factor-β dependent.
abstract: 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™), 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™ 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™ (OVA/ASHMI™) or water (OVA/sham) for 4 weeks, and then challenged immediately and 8 weeks post-therapy. In other experiments, OVA mice received ASHMI™ treatment with concomitant neutralization of IFN-γ or TGF-β. 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™ 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-γ levels also persisted at least 8 weeks post-therapy. ASHMI™ effects were eliminated by the neutralization of IFN-γ, but not TGF-β, during therapy.
  
  
  CONCLUSIONS
  ASHMI™ induced long-lasting post-therapy tolerance to antigen-induced inflammation and AHR. IFN-γ is a critical factor in ASHMI™ effects.
authors.affiliation: Department of Pediatrics, Division of Allergy & Immunology, The Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, NY 10029-6574, USA.
authors.forename: K
authors.initials: K
authors.lastname: Srivastava
authors.forename: T
authors.initials: T
authors.lastname: Zhang
authors.forename: N
authors.initials: N
authors.lastname: Yang
authors.forename: H
authors.initials: H
authors.lastname: Sampson
authors.forename: X M
authors.initials: XM
authors.lastname: Li
mesh_terms: D000818:Animals; D018927:Anti-Asthmatic Agents / Q000494:pharmacology*; D000906:Antibodies / Q000008:administration & dosage; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D016535:Bronchial Hyperreactivity / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D001985:Bronchial Provocation Tests; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D005260:Female; D007073:Immunoglobulin E / Q000097:blood; D007371:Interferon-gamma / Q000378:metabolism*; D008168:Lung / Q000187:drug effects* / Q000276:immunology / Q000503:physiopathology; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin; D011014:Pneumonia / Q000188:drug therapy / Q000276:immunology; D011657:Pulmonary Eosinophilia / Q000188:drug therapy / Q000276:immunology; D018418:Th2 Cells / Q000187:drug effects* / Q000276:immunology; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000378:metabolism*
chemical_list: C555782:ASHMI herbal formula; D018927:Anti-Asthmatic Agents; D000906:Antibodies; D004365:Drugs, Chinese Herbal; D016212:Transforming Growth Factor beta; D007073:Immunoglobulin E; D007371:Interferon-gamma; D010047:Ovalbumin