Relationship of arachidonic acid metabolism to indomethacin-sensitive immunoregulatory function and lymphocyte PGE sensitivity in peripheral blood mononuclear cells of disseminated solid tumor cancer patients.

Abstract

The relationship between the conversion of arachidonic acid (AA) to E series prostaglandins (PGE), indomethacin-sensitive immunoregulation and lymphocyte PGE sensitivity was investigated in the peripheral blood mononuclear cells (PBMC) of normal subjects and disseminated solid tumor patients. Production of PGE was assessed by thin layer chromatography of ether-extracted glass adherent cells following a 24-hour pulse with 3H-AA. Immunoregulatory cell function was assessed in PHA-stimulated PBMC cultured in the presence of the prostaglandin synthetase inhibitor, indomethacin. Lymphocyte PGE sensitivity was assessed in PHA stimulated glass nonadherent cells cultured in the presence of 10(-8) M PGE. The cells from cancer patients demonstrated greater AA conversion to PGE and greater indomethacin sensitive immunoregulatory cell function than the cells of normal subjects. However, lymphocyte PGE sensitivity was comparable for both groups. When levels of arachidonic acid conversion to PGE were correlated to levels of indomethacin-sensitive immunoregulatory cell function by linear regression analysis, a significant correlation was found. These data suggest that the increased indomethacin-sensitive immunoregulatory cell function seen in PBMC from cancer patients can be directly correlated with increased production of E series prostaglandins by cancer patient peripheral blood monocytes.