Effect of endogenous interleukin-6 on Fas (APO-1/CD95) receptor expressionin advanced melanoma patients

Interleukin-6 (IL-6) has been shown to support either autocrine or paracrin e growth in melanoma, and may prevent programmed cell death in different ce ll types. We have previously demonstrated that the endogenous IL-6 level is significantly correlated with tumor burden and nonresponse to biochemother apy in metastatic malignant melanoma patients. In the present study, we inv estigated the relationship between endogenous IL-6 and apoptosis signal thr ough Fas (APO-1/CD95) receptor expression in 9 responder and 15 refractory patients with metastatic disease treated by biochemotherapy. Before any tre atment, double immunostaining demonstrated that 61.5% of the tumor cells we re HMB45(+)CD95(+). At day 49 in refractory patients, a significant decreas e (p = 0.04) of total Fas expression was observed. Furthermore, a significa nt reduction (p = 0.032) in the percentage of HMB45(+)CD95(+) cells occurre d. An 11-fold increase in serum IL-6 level was detected (p < 0.002). This i ncrease was negatively correlated (r= -0.2, p = 0.008) with the decrease in total Fas expression. However, in responding patients, no detectable decre ase in Fas expression was observed, while a very low increase in serum IL-6 (2-fold) was detected. These results suggest that the increased endogenous IL-6 level in refractory patients may inhibit apoptosis via modulation of Fas expression. These preliminary results must be interpreted with caution, and further study with a greater number of patients is needed to understan d the mechanism by which IL-6 inhibits apoptosis in melanoma.