IMMUNE MODULATORY EFFECTS OF INDOMETHACIN IN MELANOMA PATIENTS ARE NOT RELATED TO PROSTAGLANDIN-E2-MEDIATED SUPPRESSION

  • 1 January 1982
    • journal article
    • research article
    • Vol. 92  (3) , 528-532
Abstract
Indomethacin significantly enhances the depressed levels of lymphocyte proliferation to the mitogens phytohemagglutinin and concanavalin A in melanoma patients. These results were related to an abnormality in prostaglandin E2 (PGE2)-mediated suppression, since this mechanism has previously been demonstrated in patients with Hodgkin''s lymphoma and with head and neck carcinoma. The results of 3 experimental approaches did not support this hypothesis. In vitro PGE2 production by cultured blood mononuclear cells was the same in 16 melanoma patients as in 45 normal controls (4.9 vs. 4.7 ng/ml). Lymphocyte sensitivity to PGE2 for melanoma patients was essentially the same as that for normal controls, since exogenous doses of PGE2 inhibited the mitogen responses to the same degree. Another prostaglandin synthetase inhibitor (RO-205720), which is structurally unrelated to indomethacin, did not augment the mitogen response in these patients. Thus, PGE2 cannot be implicated as a mediator of immunosuppression in melanoma patients. To further examine the immunomodulatory mechanism of indomethacin, the drug was preincubated with purified populations of lymphocytes or monocytes, which were then recombined and tested for mitogen resposne. Indomethacin probably had a direct effect on the responding T lymphocytes rather than an indirect effect on monocytes. These are the first studies demonstrating that indomethacin can act directly as a modulator of cellular immune function, independent of PGE2-mediated suppression.