In vitro production of TNF-alpha, IL-1 beta and IL-6 by mononuclear blood cells of patients with renal cell carcinoma undergoing rIL-2 treatment. Relation between clinical response and TNF-alpha production.

The purpose of this study was to examine the production of IL-1 beta, IL-6 and TNF-alpha by peripheral blood mononuclear cells in patients with renal cell carcinoma treated with recombinant interleukin 2 (rIL-2). Peripheral blood mononuclear cells (PBMC) were purified from blood samples obtained six times during therapy and the production of IL-1 beta, IL-6 and TNF-alpha were determined after 18 h culture of the PBMC in culture medium or in medium containing 10 micrograms lipopolysaccharide (LPS)/ml, 10 ng LPS/ml or 1000 units rIL-2/ml. In vivo therapy with rIL-2 resulted in substantial changes in the production of the three cytokines. Only the production of TNF-alpha following in vitro stimulation with rIL-2 was related to the clinical response, being significant lower in responding patients than in non-responders (P less than 0.05). These findings suggest that the rIL-2-induced TNF-alpha production of PBMC in vitro is lower in renal cancer patients that respond to rIL-2 therapy than in non-responding patients.