難治性喘息の病態と治療に関する研究　第2編　難治性喘息における細胞反応型アレルギーに対する選択的 Thromboxane A(2) 合成酵素阻害剤の抑制機序について

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), TXA2 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 blastgenesis, but did not suppress significantly interleukin-2 (IL-2) or neutrophil chemotactic factor (NCF) production. Furthermore, STA(2) increased lymphocyte blastgenesis stimulated by Candida antigen partially, but not dose-dependently. On the other hand, PGE(2) suppressed significantly lymphocyte blastgenesis 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.

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