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

Objectives Interleukin-6 (IL-6) is evaluated as a candidate mediator of morbidity in patients with metastatic adenocarcinoma of the prostate. Methods. IL-6 concentration is measured by enzyme-linked immunoadsorbent assay (ELISA) in the ejaculate plasma of healthy men, in primary culture of prostate epithelial cells, in human prostate cancer cell line cultures and SCID mouse xenografts, and in the plasma of 73 men with metastatic adenocarcinoma of the prostate. Results. High levels of IL-6 secretion are found in the normal human ejaculate, in prostate epithelial primary culture, and in three of four anaplastic, androgen-independent human prostate cancer cell lines tested. In contrast, the hormone-responsive and PSA-secreting cell lines and the hormone-independent line PPC-1 do not secrete detectable levels of IL-6 by ELISA. The acquisition of a p53 mutation in LNCaP-GW and PPC-1 is not sufficient to 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 levels of IL-6. Plasma IL-6 levels have a bimodal distribution, with the 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 data show that IL-6 is a prostate exocrine gene product, a candidate mediator of prostate cancer morbidity, and a candidate marker of disease activity for prospective clinical testing.