Regulation of Human Eotaxin Generation by Th1-/Th2-Derived Cytokines

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Abstract
Background: Accumulating evidence indicates that eotaxin is the primary mediator of tissue eosinophilia. In the present study, we analyzed the mechanisms of eotaxin generation by Th1-/Th2-derived cytokines in vitro. Methods: Human dermal fibroblasts, human umbilical vein endothelial cells and A549 human bronchial epithelial cell line cells were stimulated with TNF-α, IL-4, IFN-γ or TNF-α in combination with IL-4 or IFN-γ and the amount of eotaxin production was analyzed. Results: Fibroblasts produced nanogram/milliliter quantities of eotaxin. Proinflammatory cytokine TNF-α and Th2-type cytokine IL-4 each induced eotaxin production, and combination of them caused a marked synergistic increase in that production. On the other hand, Th1-type cytokine IFN-γ inhibited eotaxin generation at the protein/mRNA levels. Conclusion: The Th2-derived cytokine upregulated while the Th1-derived cytokine inhibited eotaxin production by fibroblasts. In view of the Th1/Th2 paradigm, these results indicate that (1) eotaxin regulates eosinophil accumulation in the Th2-dominant state such as allergic disease, and (2) direct suppression of eotaxin production by IFN-γ is one of the major mechanisms by which IFN-γ suppresses eosinophilic inflammation.