Immunosuppressive effect of leukotriene B(4) receptor antagonist in vitro.

Leukotriene B(4) (LTB(4)), which is an arachidonic acid metabolite produced by the 5-lipoxygenase pathway and a well-characterized chemical mediator of inflammation, has been proposed to be an immune response modulator. Here we showed the constitutive expression of the LTB(4) receptor (LTB(4)R) in resting and activated T cells. We found that the LTB(4)R antagonist inhibited T cell proliferation induced by Con A, immobilized anti-CD3 mAb, or IL-2. This inhibitory effect was abolished by addition of LTB(4)R agonist. The LTB(4)R antagonist inhibited IL-2, IFN-gamma, and IL-4 production by anti-CD3-stimulated T cells and also inhibited IL-12-induced IFN-gamma production. Moreover, the LTB(4)R antagonist exerted an additive inhibitory effect to FK506 on T cell proliferation. These results suggest that LTB(4) is intrinsically involved in T cell activation to upregulate cytokine production and proliferation, and thus the LTB(4)R antagonist might be useful as an immunosuppressive agent.