Indomethacin abrogates the suppression by cyclosporin A of lectin-dependent cell-mediated cytotoxicity to HEp-2 cells.
The effects of cyclosporin A, prostaglandin E1 and indomethacin were studied on lectin-dependent cell-mediated cytotoxicity (LDCC) against adherent HEp-2 human epipharynx carcinoma target cells. LDCC activity by human peripheral blood lymphocytes was evaluated by detachment from the monolayer of [3H]thymidine-prelabelled HEp-2 cells in a 24-h assay at 50:1 effector:target cell ratio in the presence of 25 micrograms/ml concanavalin A. Under these conditions, but without concanavalin A, considerable natural cell-mediated cytotoxicity was not elicited although LDCC was significantly augmented in the presence of concanavalin A. Addition of both cyclosporin A (0.1, 1.0 or 10 micrograms/ml) and prostaglandin E1 (10(-8), 10(-7) or 10(-6) M) dose-dependently suppressed LDCC activity. Indomethacin (0.1, 1.0 or 10 micrograms/ml) did not in itself influence LDCC although suppression of LDCC by cyclosporin A, but not prostaglandin E1, was abrogated in the presence of indomethacin. Similar to indomethacin, acetyl salicylic acid also reversed the inhibition of LDCC by cyclosporin A. In parallel experiments, cyclosporin A elicited a more than two-fold increase of prostaglandin E production under LDCC assay conditions as measured by radioimmunoassay. Contrary to LDCC, depression of concanavalin A induced blastogenesis by cyclosporin A was not influenced by indomethacin, suggesting that the inhibition by cyclosporin A of LDCC and concanavalin A-induced blastogenesis proceed via different mechanisms.
D002294:Carcinoma, Squamous Cell; D002460:Cell Line; D003208:Concanavalin A; D003524:Cyclosporins / Q000494:pharmacology*; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D004336:Drug Antagonism; D006801:Humans; D007165:Immunosuppression Therapy; D007213:Indomethacin / Q000494:pharmacology*; D008214:Lymphocytes / Q000276:immunology*; D011458:Prostaglandins E / Q000032:analysis; D011863:Radioimmunoassay
D003524:Cyclosporins; D011458:Prostaglandins E; D003208:Concanavalin A; D007213:Indomethacin