Studies on the mechanism and treatment of intractable asthma

Part 2. The mechanism of specific thromboxane A₂ synthetase inhibitor in cell-mediated allergy in intractable asthmatics

Abstract

The specific thromboxane A₂ (TXA₂) 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 TXA₂ and prostaglandin E₂ (PGE₂) in cell-mediated allergy, the effect of the TXA₂ receptor antagonist (AA-2414), TXA₂ analogue (STA₂) and PGE₂ for peripheral blood mononuclear cells in adult intractable asthmatics was studied.
OKY-046 significantly suppressed TXB₂ production and increased PGE₂ 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, STA₂ increased lymphocyte blastogenesis stimulated by Candida antigen partially, but not dose-dependently. On the other hand, PGE₂ 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 TXA₂ and PGE₂ play an important role in the mechanism of intractable asthma.