Effect of indomethacin on the release of chemical mediators from human peripheral leukocytes

We studied the effect of indomethacin (IND) on the release of chemical mediators from human peripheral leukocytes and the relation of prostaglandin (PG) E2 and PGI2 to that effect. We stimulated the leukocyte suspensions with calcium ionophore A23187 (CaI, 10(-6) M) accompanied with IND (10(-5) M), PGE2 (10(-5) M) or PGI2 (10(-5) M) and measured the levels in histamine (HA), leukotriene C4/D4/E4 (peptide-LTs) and LTB4 in the supernatant fluid. The increase of HA levels induced by CaI was significantly enhanced by IND (p < 0.01), and the enhancement was significantly inhibited by PGE2 (p < 0.05) and PGI2 (p < 0.01). The release of peptide-LTs was not enhanced by IND and was inhibited significantly by PGE2 (p < 0.05) and PGI2 (p < 0.01). IND did not affect the release of LTB4 induced by CaI. However, LTB4 release was also significantly inhibited by PGE2 and PGI2 (p < 0.01). These results suggest that the inhibitory effect of IND on the production of PGE2 and PGI2 results in the enhancement of HA release. PGE2 and PGI2 have a potent inhibitory effect on the release of HA, peptide-LTs and LTB4 from human leukocytes.