INDUCTION OF LYMPHOKINE-ACTIVATED KILLER ACTIVITY IN MICE BY PROTHYMOSIN-ALPHA

We have recently demonstrated that prothymosin alpha (ProTalpha) when administered intraperitoneally (i. p.) protects DBA/2 mice against the growth of syngeneic leukemic L1210 cells through the induction of tumoricidal peritoneal cells producing high levels of tumor necrosis factor alpha (TNFalpha) [Papanastasiou et al. (1992) Cancer Immunol Immunother 35: 145]. In this report we tested further immunological alterations that may be caused by the administration of ProTalpha in vivo. We demonstrate that i. p. injections of ProTalpha enhance natural killer (NK) cell activity and induce lymphokine-activated (LAK) activity in vivo. Thus, splenocytes from ProTalpha-treated DBA/2 animals exhibited significantly higher cytotoxic activity (up to threefold) against the NK-sensitive YAC cell line and the NK-resistant P815 and L1210 syngeneic tumor cells, as compared to splenocytes from syngeneic control mice. The enhancement of the cytotoxic profile of DBA/2 splenocytes was associated with increased percentages of CD8+ cells, NK cells and activated CD3+ cells. The ProTalpha-induced effect persisted for 30 days after the end of the ProTalpha treatment period and returned to normal levels 20 days later. Splenocytes from non-treated DBA/2 animals generated high NK and LAK activities in response to ProTalpha in vitro. The ProTalpha-induced NK an LAK activities reached 84% and 75% respectively of what was obtained with interleukin2 (IL-2). High concentrations of TNFalpha and IL-2 were generated in response to ProTalpha in LAK cultures. These findings suggest that ProTalpha may provide an overall protective effect against tumor growth in vivo through induction of NK and LAK activities possibly indirectly via the production of IL-2 and TNFalpha in the spleen, peritoneal cavity and probably other lymphoid organs.