Abnormal indomethacin-sensitive suppression in peripheral blood mononuclear cells of cancer patients restricts augmentation by interleukin-2.
The capacity of the immunomodulators interleukin-2 (IL-2) and indomethacin to augment phytohemagglutinin (PHA)-induced lymphoproliferation in the peripheral blood mononuclear cells (PBMC) of cancer patients was evaluated. Ficoll-Hypaque-isolated PBMC from 20 patients with disseminated non-lymphoreticular solid tumors were stimulated with PHA in the presence of IL-2, indomethacin, or IL-2 plus indomethacin. Augmentation of PHA responsiveness by each immunomodulator was additive. There was a significant negative correlation between PHA reactivity and immunomodulation by indomethacin. There was no correlation between PHA reactivity and immunomodulation by IL-2. A significant negative correlation was also found between indomethacin-induced augmentation and IL-2-induced augmentation in patients with significantly impaired reactivity to PHA. Still, the combined effects of IL-2 and indomethacin could not prevent the suppressive effects of prostaglandin E2 added to PHA-stimulated cultures containing both immunomodulators. These results suggest that the presence of abnormal indomethacin-sensitive immunoregulation in PBMC from cancer patients limits lymphocyte responsiveness to IL-2 and suggests that these two immunomodulators might be combined in certain cancer patient therapies.
D000328:Adult; D000368:Aged; D015232:Dinoprostone; D006801:Humans; D007167:Immunotherapy; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology*; D007376:Interleukin-2 / Q000276:immunology*; D008213:Lymphocyte Activation; D008875:Middle Aged; D009369:Neoplasms / Q000276:immunology* / Q000628:therapy; D010835:Phytohemagglutinins / Q000494:pharmacology; D011458:Prostaglandins E / Q000494:pharmacology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000276:immunology
D007376:Interleukin-2; D010835:Phytohemagglutinins; D011458:Prostaglandins E; D015232:Dinoprostone; D007213:Indomethacin