Regulation of human eotaxin generation by Th1-/Th2-derived cytokines

Background: Accumulating evidence indicates that eotaxin is the primary med iator of tissue eosinophilia. In the present study, we analyzed the mechani sms of eotaxin generation by Th1-/Th2-derived cytokines in vitro. Methods: Human dermal fibroblasts, human umbilical vein endothelial cells and A549 h uman bronchial epithelial cell line cells were stimulated with TNF-alpha, I L-4, IFN-gamma or TNF-alpha in combination with IL-4 or IFN-gamma and the a mount of eotaxin production was analyzed. Results: Fibroblasts produced nan ogram/milliliter quantities of eotaxin. Proinflammatory cytokine TNF-alpha and Th2-type cytokine IL-4 each induced eotaxin production, and combination of them caused a marked synergistic increase in that production. On the ot her hand, Th1-type cytokine IFN-gamma inhibited eotaxin generation at the p rotein/mRNA levels. Conclusion: The Th2-derived cytokine upregulated while the Th1-derived cytokine inhibited eotaxin production by fibroblasts. In vi ew of the Th1/Th2 paradigm, these results indicate that (1) eotaxin regulat es eosinophil accumulation in the Th2-dominant state such as allergic disea se, and (2) direct suppression of eotaxin production by IFN-gamma is one of the major mechanisms by which IFN-gamma suppresses eosinophilic inflammati on. Copyright (C) 2000 S. Karger AG, Basel.