The specific thromboxane A
2 (TXA
2) synthetase inhibitor (OKY-046) seems to be a useful drug in the treatment of intractable asthmatics. In this study, to clarify the action mechanism of OKY-046 and the relationship between TXA
2 and prostaglandin E
2 (PGE
2) in cell-mediated allergy, the effect of the TXA
2 receptor antagonist (AA-2414), TXA
2 analogue (STA
2) and PGE
2 for peripheral blood mononuclear cells in adult intractable asthmatics was studied.
OKY-046 significantly suppressed TXB
2 production and increased PGE
2 production from the peripheral blood mononuclear cells stimulated by PHA and Candida antigen, but AA-2414 had no effect. AA-2414 suppressed lymphocyte blastogenesis, but did not suppress significantly interleukin-2 (IL-2) or neutrophil chemotactic factor (NCF) production. Furthermore, STA
2 increased lymphocyte blastogenesis stimulated by Candida antigen partially, but not dose-dependently. On the other hand, PGE
2 suppressed significantly lymphocyte blastogenesis and IL-2 and NCF production in a dose-dependent manner.
These findings suggest that the action mechanism of OKY-046 is a suppressive effect of cell-mediated allergy, and that TXA
2 and PGE
2 play an important role in the mechanism of intractable asthma.
View full abstract