Indomethacin-induced augmentation of lymphoproliferative responses in patients with head and neck cancer.
Augmentation of the phytohemagglutinin (PHA)-induced lymphoproliferation of peripheral blood mononuclear cells by indomethacin, a drug which blocks prostaglandin (PG) synthesis, was assessed in 37 patients with squamous cell carcinoma of the head and neck. Indomethacin enhanced the uptake of 3H-thymidine in stimulated cultures both from patients and normal individuals. However, because lymphoid cells from cancer patients were less reactive than those from normal controls, the proportionate increase in PHA-stimulated 3H-thymidine incorporation caused by indomethacin was greater in this population than in the normal population. The degree of enhancement induced by indomethacin did not correlate with the percent of esterase-positive mononuclear cells in the preparations. The amounts of PGE synthesized at 48 h by patients' or normal cells were similar. Cell populations that exhibited elevated levels of augmentation in the presence of indomethacin were approximately 3 times as sensitive to inhibition by 3 nM PGE2. The degree of augmentation detected in the presence of Ro-20-5720, which also prevents PG synthesis, was related to that produced by indomethacin. These results suggested that: the enhancing effect of indomethacin on lymphoproliferation in vitro was related to its inhibition of PG synthesis; and the sensitivity of lymphoid cells to inhibition by PGE2 was slightly, but significantly, increased in individuals with elevated augmentation values.
McCormick
K J
KJ
Panje
W R
WR
D000328:Adult; D000368:Aged; D002227:Carbazoles / Q000494:pharmacology; D002294:Carcinoma, Squamous Cell / Q000276:immunology*; D015232:Dinoprostone; D004950:Esterases / Q000032:analysis; D006258:Head and Neck Neoplasms / Q000276:immunology*; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects*; D008875:Middle Aged; D009000:Monocytes / Q000201:enzymology; D010835:Phytohemagglutinins / Q000494:pharmacology; D011458:Prostaglandins E / Q000096:biosynthesis / Q000494:pharmacology
D002227:Carbazoles; D010835:Phytohemagglutinins; D011458:Prostaglandins E; D004950:Esterases; C007005:carprofen; D015232:Dinoprostone; D007213:Indomethacin