We have previously demonstrated that human renal cell carcinoma (RCC) cells express high-affinity IL-4 receptors (IL-4R). To study the functions
of these receptors, we have examined the effect of IL-4 on the expression of intercellular adhesion molecule-I (ICAM-I or CD54) on human RCC cells. Following incubation with various concentrations of IL-4, RCC cells were examined for ICAM-I expression by flow cytometric analysis. The 2 primary RCC cell cultures and the 2 cell lines examined expressed varying basal levels of ICAM-I on the cell surface. 11-4 treatment increased ICAM-I expression in a time-dependent manner and maximum augmentation of ICAM-I expression was observed after a 48 hr incubation. The increase in ICAM-I expression was specific because anti-hlL-4 antibody blocked this effect. No enhancement of ICAM-I expression was observed when RCC cells were incubated with IL-4 in the presence of cycloheximide, indicating that the IL-4 effect requires new protein synthesis. Up-regulation of ICAM-I expression was also observed at the mRNA level and maximum increase in message occurred 8 hr post-114 treatment. Both IL-4 and IFN-y also increased soluble ICAM-I levels in WS-RCC culture supernatant. The significance of enhanced soluble and surface ICAM-I expression was investigated by examining the lymphokine activated killer (LAK) cell-mediated lysis of IL-4treated WS-RCC cells. LAK cells lysed WS-RCC cells very effectively, but lysis observed in target cells pre-treated with IL-4 did not correlate with the increased expression of ICAM-I antigen. Our results indicate a previously unknown function of IL-4 on RCC and further demonstrate that IL-4R on RCC are functional.