The differential expression of proinflammatory cytokines IL-6, IL-8 and TNF-alpha in renal cell carcinoma.

Recent observations indicate that an antiinflammatory process may play a role in the metastatic cascade of renal cell carcinoma (RCC). Therefore, we compared the expression of cytokines from primary human RCC cultures, from established renal carcinoma cells and those from corresponding proximal renal tubulus cells. For this purpose the different cell types were treated with well defined and with bacterial substances such as the lipopolysaccharide, the staphylococcal enterotoxin B, a superantigen, or a combination of the calcium ionophore A23187 and phorbol 12-myristate-13-acetate. The resulting cell supernatants were analyzed for the proinflammatory cytokines (TNF-alpha, IL-6), the chemotactic active interleukin-8 as well as cytokines from T-helper type I (IL-2, IFN-gamma, IL-12) and type II (IL-4, IL-10). In parallel, the expression of cytokine-specific m-RNA was analyzed by multiplex-PCR. Our results clearly demonstrate that among the various cytokines analyzed a predominant release of TNF-alpha, IL-8 and IL-6 is obtained. The remainder cytokines were not detected independent whether molecular biology or cytokine release experiments were applied. Expression of the cytokines was dependent on the degree of malignancy. Among the applied stimuli, only the activation with calcium ionophore/phorbolester modulated cytokine expression and release. While TNF-alpha was induced from normal renal cells by up to 300% (2000 + 120 ng/10(5) cells) a pronounced suppression of TNF-alpha was observed in dependence on the malignancy of the cell line. In contrast, the cytokines IL-6 and IL-8 were significantly upregulated in malignant cells unlike in normal renal cells. These data suggest a differential role of the various cytokines derived from normal or tumor cells. Detailed studies will allow the understanding of the distinct roles of cytokines in renal carcinoma disease.