Identification of the inhibitory p40 subunit of interleukin 12 from the ascitic fluid of patients with advanced carcinoma of the ovary

Abstract

DeCesare SL, Gamero A, Becker J, Barton D, Bomalaski J, Fiorica J, Arango H, Hoffman M, Djeu J. Identification of the inhibitory p40 subunit of interleukin 12 from the ascitic fluid of patients with advanced carcinoma of the ovary. Int J Gynecol Cancer 1988; 8: 133–137. Objective: To determine the levels of interleukin 12 (IL-12) in the ascites from patients diagnosed with advanced epithelial ovarian cancer. Methods: Ascites samples from advanced ovarian cancer patients and peritoneal fluid from normal controls and endometriosis patients were tested for the presence of IL-12 by ELISA. Two different IL-12 ELISA kits were used. One ELISA kit detected the bioactive heterodimeric form of the IL-12 cytokine composed of the p40 and p35 subunits, while the second kit detected both the bioactive form and the p40 subunit of IL-12. Results: The first ELISA, which tested for only the bioactive heterodimer of IL-12, was negative in all 28 ovarian cancer patients. The second ELISA assay, which reacts with both the p40 subunit monomer and the heterodimer of IL-12, showed detectable levels of IL-12 in all 28 cancer patients and all 29 benign patients. Since no IL-12 heterodimer was detected in the first assay, these results represented the p40 monomer levels. A significantly higher median level of IL-12 monomer was found in malignant ascites compared to all benign control groups (P < 0.05). Conclusions: Ascites from advanced ovarian cancer patients contains significantly higher levels of the IL-12 p40 subunit than peritoneal fluid from normal patients, but contains no measurable bioactive IL-12 heterodimer. The secreted p40 subunit has been shown to inhibit IL-12 mediated activation of T and natural killer cells in vitro. In vivo suppression of lymphocytes by IL-12 p40 in ovarian cancer patients has not yet been demonstrated.