Th1-derived cytokine IFN-gamma is a potent inhibitor of eotaxin synthesis in vitro.

Eotaxin potentially plays an integral role in tissue eosinophilia. Inasmuch as Th2-derived cytokine IL-4 has been shown to stimulate eotaxin generation, we investigated here the effect of Th1-derived cytokine IFN-gamma on human eotaxin production. IFN-gamma but not -alpha or -beta potently inhibited tumor necrosis factor (TNF)-alpha-induced eotaxin generation by dermal fibroblasts. The inhibitory effect was unique to eotaxin, because production of IL-8 or monocyte chemoattractant protein (MCP)-1 protein was not affected by the treatment with IFN-gamma. Furthermore, the suppressive effect of IFN-gamma was not cell-type or stimulus specific. The level of eotaxin mRNA increased within 2 h after activation with TNF-alpha and continued to increase up to 72 h. IFN-gamma did not inhibit, but rather augmented the TNF-alpha-induced accumulation of mRNA in the early phase ( approximately 6 h). However, in the later phase, IFN-gamma completely prevented the subsequent elevation of eotaxin mRNA and sustained it at low levels. Although the protective effect of IFN-gamma against allergic inflammation has been assumed to result from its sole regulation of the proliferation of Th2-type T lymphocytes, these results imply that IFN-gamma can also directly act on stromal cells to inhibit eotaxin production and consequently intervene in eosinophil recruitment.