Altering the Th1/Th2/Th17 balance as a therapeutic option for refractory asthma

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GATA-3-overexpressing mice exhibited steroid-sensitive eosinophilic inflammation under Th2-biased conditions and RORgammat-overexpressing mice developed steroid-insensitive neutrophilic inflammation under Th17-biased conditions. The levels of KC, MIP-2, IL-6 and other neutrophil chemotaxis-related mediators were significantly elevated in OVA-exposed RORgammat-overexpressing mice, compared with wild-type mice. Interestingly, airway hyperresponsiveness accompanied by neutrophilic airway inflammation in RORgammat-overexpressing mice was effectively suppressed by anti-IL-17 antibody, CXCR2 antagonist or anti-IL-6 receptor antibody administration. In conclusion, our results suggest that the expression levels of GATA-3 and RORgammat may be important for determining the phenotype of asthmatic airway inflammation. Furthermore, blockade of the Th17 signaling pathway may be a treatment option for steroid-insensitive asthma.