Interferon-gamma inhibits in vitro mobilization of eosinophils by interleukin-5.

ABSTRACT

BACKGROUND: Th2 cytokines play pivotal roles in allergic inflammation, including eosinophilia, and their actions are antagonized by Th1 cytokines, conferring them therapeutic potential. METHODS: In this study, we examined the ability of a number of cytokines to suppress the activation of eosinophils that function as effector cells for allergic airway diseases. RESULTS: Interleukin (IL)-5, IL-6, and tumor necrosis factor (TNF) induced an eosinophil shape change, whereas interferon (IFN)-gamma significantly inhibited the shape change. Other cytokines, including IL-1beta, IL-4, IL-10 and IL-13, had little or only slightly enhancing or reducing effects on the shape change. We further analyzed the IFN-gamma effect, showing that pretreatment with IFN-gamma strongly suppressed IL-5-induced eosinophil shape change, and cycloheximide (CHX) abrogated the suppression by IFN-gamma, suggesting that new protein synthesis is required for the inhibitory effect by this cytokine. In agreement with these results, IFN-gamma blocked the eosinophil migration and ERK phophorylation induced by IL-5, and the addition of CHX restored eosinophil chemotaxis. CONCLUSIONS: Collectively, IFN-gamma may attenuate eosinophilic inflammation by directly negating eosinophil mobilization.