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International Immunology, Vol. 11, No. 6, 1001-1004, June 1999
© 1999 Japanese Society for Immunology

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

Misato Miyamasu, Masao Yamaguchi, Toshiharu Nakajima1, Yoshikata Misaki, Yutaka Morita, Kouji Matsushima2, Kazuhiko Yamamoto and Koichi Hirai1

Department of Allergy and Rheumatology,
1 Department of Bioregulatory Function, and
2 Department of Molecular Preventive Medicine and CREST, University of Tokyo Graduate School of Medicine, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan

Correspondence to: K. Hirai

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 -ß 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 (~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.

Keywords: allergy, ELISA, eosinophil, fibroblast, IL-4

Transmitting editor: K. Sugamura


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