Interleukin-6 and TNF alpha production in human renal cell carcinoma

Several clinical and biological features suggest that cytokines implicated in the inflammatory response are produced by renal cell carcinoma (RCC). To define if alterations of tumor necrosis factor alpha (TNF alpha), interleukin 1 alpha (IL-1 alpha), IL-1 beta and IL-6 gene expression are present in this malignancy, samples from 19 tumors as well as samples from seven paired normal renal tissue were examined using Northern blot and immunohistochemical analysis. In addition, the expression of these cytokines was evaluated in seven RCC-derived cell cultures using Northern blot or RT-PCR. TNF alpha and IL-6 proteins were measured in culture supernatants using specific bio- and immunoassays. Consistent levels of IL-6 mRNA were detected in 17 of the 19 tested tumors whereas TNF alpha specific transcripts were present in seven of eight available RNA samples. TNF alpha and IL-6 mRNA were also detected in five of the seven paired normal kidneys. By immunolabeling, IL-6 antigen was not detected in RCC cells in any of the 19 studied samples. In contrast, using anti-TNF alpha antibody a strong labeling of stromal endothelia and macrophage cells was detected in all the 19 cases, and evident TNF alpha staining of the carcinoma cells themselves was observed in eight cases. Spontaneous IL-6 mRNA expression was detected in five RCC cell cultures and TNF alpha mRNA in four. The cultured cells exhibited positive TNF alpha immunolabeling in six of seven cases but were always IL-6 negative. Bioactive IL-6 was detected in all culture supernatants while bioactive TNF alpha was not detected.(ABSTRACT TRUNCATED AT 250 WORDS)