HIGH SERUM LEVELS OF SOLUBLE IL-2 RECEPTOR, CYTOKINES, AND C-REACTIVEPROTEIN CORRELATE WITH IMPAIRMENT OF T-CELL RESPONSE IN PATIENTS WITHADVANCED EPITHELIAL OVARIAN-CANCER

The serum levels of interleukin-(IL-)1 alpha, IL-1 beta, IL-2, IL-6, T NF alpha, and sIL-2R and the proliferative response of peripheral bloo d mononuclear cells (PBMC) to phytohemagglutinin (PHA), anti-CD3 monoc lonal antibody (mAb), recombinant IL-2 (rIL-2), and the combination of PHA or anti-CD3 mAb with rIL-2 were studied and correlated with serum levels of C-reactive protein (CRP) in women with advanced epithelial ovarian cancer. The expression of CD25 and CD122 subunities of membran e-bound IL-2R on PHA- or anti-CD3 mAb-stimulated PBMC was also studied . In comparisons with the controls, PBMC response to PHA, anti-CD3 mAb , and rIL-2 was significantly lower in the cancer patients. The additi on of exogenous rIL-2 to the PBMC cultures increased response in both controls and patients but did not modify the significance of the diffe rences. After stimulation with PHA or anti-CDS mAb, the percentage of PBMC CD25(+) or CD122(+) was significantly lower in patients. The seru m levels of IL-1 alpha, IL-1 beta, IL-6, TNF alpha, sIL-2R, and CRP we re significantly increased in patients compared to the controls. Inste ad, no differences were observed for serum levels of IL-2. A strong as sociation was found between high serum levels of the above-mentioned c ytokines, sIL-2R, and CRP. The results of our study on advanced stage (IIIb-IV) ovarian cancer patients are consistent with the previously r eported hypothesis that high IL-6 and/or CRP serum levels may represen t an important and independent prognostic factor of the likely outcome in cancer patients. (C) 1998 Academic Press.