Rationale: Asthma is characterized by increases in airway resistance, pulmonary remodeling, and lung inflammation. The cytokine transforming growth factor (TGF)-b has been shown to have a central role in asthma pathogenesis and in mouse models of allergic airway disease. Objectives: To determine the contribution of TGF-b to airway hyperresponsiveness (AHR), we examined the time course, source, and isoform specificity of TGF-b production in an in vivo mouse asthma model. To then elucidate the function of TGF-b in AHR, inflammation, and pulmonary fibrosis, we examined the effects of blocking TGF-b signaling with neutralizing antibody. Methods: Mice were sensitized and challenged with ovalbumin (OVA) to establish allergic airway disease. TGF-b activity was neutralized by intranasal administration of monoclonal antibody. Measurements and Main Results: TGF-b1 protein levels were increased in OVA-challenged lungs versus naive controls, and airway epithelial cells were shown to be a likely source of TGF-b1. In addition, TGF-b1 levels were elevated in OVA-exposed IL-5-null mice, which fail to recruit eosinophils into the airways. Neutralization of TGF-b1 with specific antibody had no significant effect on airway inflammation and eosinophilia, although anti-TGF-b1 antibody enhanced OVAinduced AHR and suppressed pulmonary fibrosis. Conclusions: These data show that TGF-b1 is the main TGF-b isoform produced after OVA challenge, with a likely cellular source being the airway epithelium. The effects of blocking TGF-b1 signaling had differential effects on AHR, fibrosis, and inflammation. While TGF-b neutralization may be beneficial to abrogating airway remodeling, it may be detrimental to lung function by increasing AHR.

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