12 P - Interleukin-8 (IL-8), interleukin-6 (IL-6), tumor necrosis factor-a (TNF-a), soluble tnf receptors (sTNFR) 75 and 55 after BCG therapy of urothelial cancer (TCC): kinetics over 6 instillations

The role of different cytokine mediators in BCG therapy of TCC is not well understood. IL-8 is a potent chemoattractant for polymorphnuclear leukocytes. IL-6 is an acute phase protein. TNF-a plays a central role in the cytokine cascade. Soluble receptors to TNF-a have been reported. After intravesical instillation of 120 mg or after perfusion of the upper urinary tract wilh 360 mg of BCG Pasteur F we measured the expression and time course of IL-8, IL-6, TNF-a and its receptors TNFR 75 and 55 during BCG therapy of TCC. Cytokines were determined by a solid phase double-ligand ELISA/ELIBA method. IL-8 titers increased to a peak of 1100ng ± 1250 (±S.D.) to 2965±1560 4–6 h after instillation with a maximum after the 5th. Over 24 h titers were highest during the first 6 h 10184 ng±4682. IL-6 attained a peak 4 h after instillations 1–5 (62ng±85 to 125ng±85) and 2 h after instillation 6 (140ng±57). Thereafter it decreased to a steady level. TNF-a reached peak values 1 h after instillation with a maximum (435ng±473) after the third. sTNFR 75 and 55 increase to a peak after 1–4 h. sTNFR 75 peak values vary from 567ng±315 to 1567ng±864, sTNFR 55 from 490ng±398 to 1222ng±1159. In the serum IL-6 titers rise 12-fold and TNF-a titers 2 fold. In conclusion, cytokines may play a mediating and modulating role in BCG antitumor activity. sTNFR 75 and 55 may antagonise or regulate TNF-a activity. Due to its properties IL-8 may prove to be an interesting parameter for BCG responsiveness.