PROSTAGLANDIN-E2-MEDIATED SUPPRESSION OF CELLULAR-IMMUNITY IN COLON CANCER-PATIENTS

  • 1 January 1984
    • journal article
    • research article
    • Vol. 95  (1) , 71-77
Abstract
The immune regulation of phytohemagglutinin (PHA) and concanavalin A (Con A) mitogen responses by prostaglandin (PG)-producing suppressor monocytes was examined in 57 patients with colorectal cancer and 55 normal individuals. Blood lymphocyte responses to either PHA or Con A were significantly depressed in 74% of patients compared to normal controls. The mean PHA response for the patients was significantly lower than that for controls (17,649 vs. 25,549 cpm, P = 0.02), while the mean Con A response for the patients was also depressed but not as significantly (13,551 vs. 18,623 cpm, P = 0.09). The depression of immune competence was greatest in older patients and those with metastatic disease. The addition of indomethacin (1 .mu.g/ml) to cell cultures of both patients and normal individuals enhanced the mitogen response, suggesting that PGE-producing suppressor cells were operative in both groups. Among the patient group, a differential modulation of the immune response by indomethacin was observed. The addition of indomethacin restored the PHA response in patients almost to normal levels, while the Con A increase was less pronounced. Even after indomethacin treatment, the Con A proliferative response by lymphocytes was significantly depressed in patients as compared to controls (P = 0.002). To prove that indomethacin was blocking excessive PG production by suppressor monocytes in colon cancer patients, PGE2 production was directly measured by peripheral blood mononuclear cells (PBMC) using a radioimmunoassay. PBMC from the patients produced significantly greater amounts of PGE2 compared to controls (10.1 vs. 5.1 ng/ml, P = 0.0001). This comparison was still significant after adjustment for age and sex. The increased PGE2 production appeared to be selective, since the levels of 2 other arachidonic acid metabolites, PGF1.alpha. and thromboxane B2, were the same or less than control levels. PG-mediated immune suppression of mitogenesis appears to be abnormally increased in colon cancer patients, particularly for the PHA response. This abnormality was partially corrected in vitro by incubation of the PBMC with indomethacin, a prostaglandin synthetase inhibitor.