Effect of indomethacin on in vitro T- and B-cell activation and cell-mediated lysis

Abstract

The effect of indomethacin, an inhibitor of prostaglandin synthetase, on lymphocyte blast transformation induced by T- or B-cell activators has been studied. Simultaneously adding indomethacin (0.03−0.3 × 10−6 M final concentration) and concanavalin A to mouse spleen cell cultures, led to an enhancement of 3H-thymidine uptake, whereas 30 × 10−6 M indomethacin inhibited this uptake. The stimulation by induced by indomethacin was higher when this drug was present in the cultures before the addition of the mitogen. Neither the optimal concanavalin A concentration nor the day on which the maximum of 3H-thymidine uptake occurred were altered by indomethacin. Activation of B lymphocytes induced by bacterial lipopolysaccharide was inhibited by indomethacin at all concentrations tested. However, indomethacin similarly blocked the prostaglandin synthesis as well in lipopolysaccharide- or concanavalin A-stimulated lymphocyte cultures. Indomethacin enhanced the one-way mixed lymphocyte reaction. No significant effect of indomethacin was found on cell-mediated cytotoxicity of 51Cr labeled targets. The results are discussed in terms of differential sensitivity of B and T lymphocytes to this anti-inflammatory drug.