Studies on the mechanism and treatment of intractable asthma Part 1. Effects of a specific thromboxane A(2) synthetase inhibitor in lymphocyte and neutrophil functions in intractable asthmatics

To clarify whether thromboxane A(2) (TXA(2)) is involved in type III and IV allergy, so-called "cell-mediated allergy", the effects of a specific TXA(2) synthetase inhibitor, sodium ozagrel (OKY-046) on peripheral blood mononuclear cells and neutrophils in adult intractable asthmatics were studied. Lymphocyte blastogenesis and interleukin-2 (IL-2) production from peripheral blood mononuclear cells stimulated by PHA and Candida antigen in intractable asthmatics was significantly suppressed dose-dependently by OKY-046. The neutrophil chemotactic factor (NCF) and eosinophil chemotactic factor (ECF) from peripheral blood nomonuclear cells stimulated by Candida antigen in intractable asthmatics tended to be suppressed by OKY-046. Furthermore, leukotriene C(4) (LTC(4)) and superoxide (O(2)(-)) production from peripheral blood neutrophils in intractable asthmatics was significantly suppressed dose-dependently by OKY-046. These findings suggest that TXA(2) plays an important role in the development of intractable asthma and OKY-046, which has a suppressive effect on type IV allergy caused by lymphocyte activation and on mediator release from neutrophils, might be a useful drug in the treatment of intractalbe asthmatics