Induction of lymphokine-activated killer activity in mice by prothymosin α.

We have recently demonstrated that prothymosin α (ProTα) 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 α (TNFα) [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 ProTα in vivo. We demonstrate that i.p. injections of ProTα enhance natural killer (NK) cell activity and induce lymphokine-activated (LAK) activity in vivo. Thus, splenocytes from ProTα-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 ProTα-induced effect persisted for 30 days after the end of the ProTα 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 ProTα in vitro. The ProTα-induced NK an LAK activities reached 84% and 75% respectively of what was obtained with interleukin-2 (IL-2). High concentrations of TNFα and IL-2 were generated in response to ProTα in LAK cultures. These findings suggest that ProTα 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 TNFα in the spleen, peritoneal cavity and probably other lymphoid organs. [ABSTRACT FROM AUTHOR]