INTERLEUKIN-6 - A CANDIDATE MEDIATOR OF HUMAN PROSTATE-CANCER MORBIDLTY

Objectives Interleukin-6 (IL-6) is evaluated as a candidate mediator o f morbidity in patients with metastatic adenocarcinoma of the prostate . Methods. IL-6 concentration is measured by enzyme-linked immunoadsor bent assay (ELISA) in the ejaculate plasma of healthy men, in primary culture of prostate epithelial cells, in human prostate cancer cell li ne cultures and SCID mouse xenografts, and in the plasma of 73 men wit h metastatic adenocarcinoma of the prostate. Results. High levels of I L-6 secretion are found in the normal human ejaculate, in prostate epi thelial primary culture, and in three of four anaplastic, androgen-ind ependent human prostate cancer cell lines tested. In contrast, the hor mone-responsive and PSA-secreting cell lines and the hormone-independe nt line PPC-1 do not secrete detectable levels of IL-6 by ELISA. The a cquisition of a p53 mutation in LNCaP-GW and PPC-1 is not sufficient t o confer the phenotype of high IL-6 secretion. Seventy-three men with well-characterized, advanced, hormone refractory prostate cancer prior to suramin therapy are tested for incidence of abnormal circulating l evels of IL-6. Plasma IL-6 levels have a bimodal distribution, with th e upper quartile of patients having abnormal levels from 9 to 61 pg/mL . A direct comparison of the high and low serum IL-6 groups shows that elevated IL-6 levels are strongly correlated with objective measures of morbidity: decreased hematocrit, hemoglobin, and serum cholesterol, and increased white blood cell count and serum lactate dehydrogenase levels all in the absence of clinical infection. Conclusions. These da ta show that IL-6 is a prostate exocrine gene product, a candidate med iator of prostate cancer morbidity, and a candidate marker of disease activity for prospective clinical testing.