The modulatory effect of antigen- and PAF-induced asthmatic reaction by aerosol administration of OKY-046 in guinea pigs.

The therapeutic effect of a thromboxane A2 (TXA2) synthetase inhibitor on asthma is still controversial. This study was aimed at clarifying its effect on asthmatic reactions in guinea pigs. Both ovalbumin (OVA)- and platelet activating factor (PAF)-induced dual phase airway spasm and hyperreactivity in guinea pigs were used as the asthma model. Our results demonstrated that aerosol administration of OKY-046 could inhibit both OVA- and PAF-induced late phase bronchoconstriction and airway hyperreactivity to methacholine in OVA sensitized guinea pigs. PAF administration could also induced dual phase bronchoconstriction in normal guinea pigs. Similarly, late phase airway spasm and airway hyperreactivity after PAF exposure was also blocked by OKY-046. In conclusion, aerosol administration of OKY-046 is a safe and effective way to modulate OVA- and PAF-induced asthmatic reactions. The protective effect of OKY-046 on OVA- and PAF-induced late phase bronchoconstriction and airway hyperreactivity indicates that TXA2 might play an important role in the late phase asthmatic reaction and airway hyperreactivity. The normalization of PAF-induced airway hyperreactivity by OKY-046 also indicates that PAF induced airway inflammation might be through the generation of TXA2.

Modulation of lymphocyte proliferation by murine liver extract.

Murine liver extract (LEx) purified by ammonium sulfate (45-70% saturation) possesses a strong inhibitory effect on human lymphocyte proliferation. We have shown that the inhibitory effect of LEx is not via a cytotoxic effect and that it is proportional to the length of incubation with LEx. Mitogen-prestimulated lymphocytes are more resistant to LEx inhibition than cells not prestimulated. B cells stimulated by PWM are more susceptible to LEx-induced inhibition than PHA- or Con A-stimulated T cells. In Con A cultures, there may be a population of cells more resistant to LEx inhibition. This population is not yet identified. The degree of reversibility of LEx inhibition was different in cells prestimulated by different mitogens. The inhibitory activity of LEx decreased in the presence of an increasing number of cells in the culture.