Thymostimulin enhances the natural cytotoxic activity of patients with transitional cell carcinoma of the bladder.

We have investigated the effect of thymostimulin on the major histocompatibility (MHC) unrestricted cytotoxic activity of peripheral blood mononuclear cells (PBMNC) from patients with superficial transitional cell carcinoma (TCC) of the bladder. PBMNC from patients and healthy controls were incubated in the presence of thymostimulin for varying periods of time (2 or 18 h or 5 days), and were used as effectors against 51Cr-radiolabeled natural killer (NK)-sensitive (K-562) and NK-resistant (JY) target cells in cytotoxic assays. In 6 out of 14 patients analyzed, thymostimulin enhanced the cytotoxic activity of PBMNC against NK-sensitive target cells in a dose-dependent manner. This cytotoxic inducer effect of thymostimulin was maximal after 18 h of culture. Thymostimulin failed to induce lytic activity in PBMNC from TCC patients against NK-resistant target cells. We also found that thymostimulin could synergize with interleukin-2 in inducing non-MHC restricted cytotoxic activity in PBMNC from TCC patients. In conclusion, we have demonstrated that thymostimulin can enhance the natural killer cytotoxic activity of PBMNC from patients with TCC of the bladder.