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 tum oricidal peritoneal cells producing high levels of tumor necrosis fact or alpha (TNFalpha) [Papanastasiou et al. (1992) Cancer Immunol Immuno ther 35: 145]. In this report we tested further immunological alterati ons 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 v ivo. 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 syngene ic tumor cells, as compared to splenocytes from syngeneic control mice . The enhancement of the cytotoxic profile of DBA/2 splenocytes was as sociated with increased percentages of CD8+ cells, NK cells and activa ted CD3+ cells. The ProTalpha-induced effect persisted for 30 days aft er the end of the ProTalpha treatment period and returned to normal le vels 20 days later. Splenocytes from non-treated DBA/2 animals generat ed high NK and LAK activities in response to ProTalpha in vitro. The P roTalpha-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 cult ures. These findings suggest that ProTalpha may provide an overall pro tective effect against tumor growth in vivo through induction of NK an d LAK activities possibly indirectly via the production of IL-2 and TN Falpha in the spleen, peritoneal cavity and probably other lymphoid or gans.