IL-4-induced apoptosis in peripheral blood eosinophils

Background: The regulation of eosinophil survival and apoptosis may play a major role in diseases demonstrating increased numbers of circulating and t issue eosinophils such as allergic reactions. Because few promoters of eosi nophil apoptosis have been described so far, the objective of this study wa s to elucidate the role of endogenous factors on eosinophil survival and ap optosis. Methods and Results: Highly purified peripheral blood eosinophils were anal yzed in the time course from 24 up to 144 hours in culture. Eosinophil surv ival was assessed with trypan blue dye exclusion and apoptosis was determin ed by DNA fragmentation gel analysis and ELISA technique with anti-histone antibodies. We confirmed previous results demonstrating prolonged eosinophi l survival and inhibited apoptosis by IL-3, IL-5, and GM-CSF. In contrast, eosinophil apoptosis was significantly enhanced by corticosteroids, particu larly dexamethasone and hydrocortisone. However IL-1 beta, IL-8, IL-12, pla telet-activating factor, TNF-alpha, and eotaxin had no effect on eosinophil survival or apoptosis when compared with culture medium alone. In contrast , IL-4 at concentrations of 100 U/mL or more inhibited eosinophil survival and induced apoptosis. This effect was time dependent and abrogated by prei ncubation with neutralizing anti-IL-4 antibodies. However, after 96 hours i n coincubation, IL-4 did overcome the survival-prolonging effect of IL-3, I L-5, and GM-CSF. IL-4 did not enhance eosinophil surface expression of APO- 1/Fas antigen (CD95), In assessing IL-4-mediated effects on eosinophil func tion, we found no response by means of the release of eosinophil cationic p rotein or reactive oxygen species. Conclusions: Taken together, our data present direct evidence for the prese nce of functional IL-4 receptors on human eosinophils and indicate that IL- 4 may lead to resolution of chronic inflammation by induction of eosinophil apoptosis.