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

Eotaxin potentially plays an integral role in tissue eosinophilia. Inasmuch as T(h)2-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. IFNr 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 IFNr 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-a-induced accumulation of mRNA in the early phase (similar to 6 h), However, in the later phase, IFNr completely prevented the subsequent elevation of eotaxin mRNA and sustained it at low levels. Although the protective effect of IFNr against allergic inflammation has been assumed to result from its sole regulation of the proliferation of T(h)2-type T lymphocytes, these results imply that IFNr can also directly act on stromal cells to inhibit eotaxin production and consequently intervene in eosinophil recruitment.