Interleukin-32γ suppresses allergic airway inflammation in mouse models of asthma.

Asthma is a chronic airway inflammatory disease typically associated with T helper cell type 2 (Th2) cytokines. IL-32, first reported as an inducer of tumor necrosis factor (TNF)-alpha, is an inflammatory cytokine involved in various autoinflammatory diseases, viral infection, and cancer-related inflammation. However, the role of IL-32 gamma in asthma has not been clearly elucidated. In this study, the levels of IL-32 gamma in sputum from patients with asthma were measured by ELISA, and IL-32 gamma function was investigated in murine models of asthma with human IL-32 gamma-overexpressed transgenic (IL-32 gamma TG) mice. The therapeutic effect of recombinant IL-32 gamma (rIL-32 gamma) on allergic inflammation was also evaluated through bronchoalveolar lavage fluid analysis and histopathologic examinations. Sputum IL-32 gamma levels from patients with asthma were lower than those from healthy control subjects. In an acute mouse model of asthma, IL-32 gamma TG mice exhibited significantly reduced airway inflammation compared with that in wild-type mice. The production of Th1 cytokines, such as TNF-alpha and IFN-gamma, and Th2 cytokines, such as IL-4, IL-5, and IL-13, was decreased in the lungs of IL-32 gamma TG mice. On the contrary, the expression of IL-10 and IL-10-producing CD11b(+) monocytic cells was significantly increased in the lungs of ovalbumin-sensitized IL-32 gamma TG mice. In addition, rIL-32 gamma treatment revealed a suppressive effect on the airway inflammation in a chronic mouse model of asthma. The results of this study suggest that IL-32 gamma may have a preventive role in the development of allergic airway inflammation and could be a potential novel therapeutic target for bronchial asthma.