Suppression of cytokine expression by roflumilast and dexamethasone in a model of chronic asthma

Background In a mouse model of mild chronic asthma, both inflammation and remodelling can be suppressed by dexamethasone (a glucocorticoid) and roflumilast (a selective phosphodiesterase‐4 inhibitor). Objective To better understand the underlying molecular mechanisms, we investigated the effects of treatment on airway expression of inflammation‐related cytokines, as well as on epithelial expression of growth factors. Methods BALB/c mice systemically sensitized to ovalbumin were challenged with aerosolized antigen for 6 weeks and treated with roflumilast or dexamethasone during the final 2 weeks. Expression of mRNA, for a variety of cytokines and growth factors, was assessed in selectively dissected proximal airways or in airway epithelium obtained by laser capture microdissection. Results In the airway wall of vehicle‐treated challenged animals, there was significantly elevated expression of mRNA for a variety of pro‐inflammatory and T helper type 2 cytokines, as well as for IFN‐γ. All these cytokines were suppressed by dexamethasone. Treatment with roflumilast reduced expression of IL‐17A, TNF‐α, granulocyte‐macrophage colony‐stimulating factor and IL‐6, but did not inhibit other cytokines. Both drugs suppressed the enhanced expression of mRNA for growth factors such as TGF‐β1 and FGF‐2 in airway epithelium. Conclusions Whereas dexamethasone non‐specifically inhibits numerous mediators involved in inflammation and the immune response, roflumilast selectively inhibits a subset of pro‐inflammatory cytokines and growth factors. These mediators and/or the cells that produce them may have critical roles in the pathogenesis of the lesions of chronic asthma.