Interleukin 4 inhibits the interleukin 2-induced production of its functional antagonist, interferon gamma.

Interferon gamma (IFN gamma) inhibits many effects of interleukin (IL)-4. Its production largely parallels cell proliferation but is regulated independently. As IL-4 inhibits several IL-2-induced effects including proliferation of human peripheral blood mononuclear cells, we investigated its influence on the IL-2-induced IFN gamma production. We found that both absolute IFN gamma production and IFN gamma production per proliferation unit (1000 cpm) in response to IL-2 were inhibited by IL-4. IL-2-induced interferon production was inhibited by IL-4 in both sheep red blood cell rosetting and non-rosetting cells. In bidirectional mixed lymphocyte culture, IL-4 alone enhanced proliferation but suppressed IFN gamma production. As 48% of IFN gamma-producing cells are known to show T cell phenotype, the nearly total inhibition of IFN gamma production is evidence for suppression of T cell response to IL-2. Additionally, we found that the inhibition of IL-2-induced proliferation by IL-4 was significantly more pronounced at low cell densities. Basal proliferation was only inhibited in serum-containing media. These data stress the importance of other lymphokines or accessory cells in the regulation of early lymphocyte activation.