p38 mitogen-activated protein kinase regulates human T cell IL-5 synthesis

Involvement of p38 mitogen-activated protein (MAP) kinase in human T cell. cytokine synthesis was investigated. p38 MAP kinase was clearly induced in human Th cells activated through the TCR, SB203580, a highly selective inhi bitor of p38 MAP kinase, inhibited the induction of p38 MAP kinase in human Th cells. Major T cell cytokines, IL-2, IL-4,-IL-5, and IFN-gamma, were pr oduced by Der f 2-specific Th clones upon stimulation through the TCR, IL-5 synthesis alone was significantly inhibited by SB203580 in a dose-dependen t manner, whereas the production of IL-2, IL-4, and IFN-gamma was not affec ted. The proliferation of activated T cells was not affected. IL-5 synthesi s of human Th clones induced upon stimulation with rIL-2, phorbol ester plu s anti-CD28 mAb, and immobilized anti-CD3 mAb plus soluble anti-CD28 mAb wa s also suppressed by SB203580 in the same concentration response relationsh ip. The results clearly indicated that IL-5 synthesis by human Th cells is dependent on p38 MAP kinase activity; and is regulated distinctly from IL-2 , IL-4, and IFN-gamma synthesis. Selective control of IL-5 synthesis will p rovide a novel treatment devoid of generalized immune suppression for bronc hial asthma and atopic dermatitis that are characterized by eosinophilic in flammation.