Augmentation of spontaneous cytotoxicity of human lymphocytes by RU 41.740 is due to monocyte-derived factors distinct from interleukin 2, interferon alpha and gamma.

In vitro exposure of human blood lymphoid cells to RU 41.740 (Biostim), a glucoprotein extract of Klebsiella pneumoniae, augments spontaneous cytotoxicity of the lymphocytes. It was observed that the augmentation could be blocked by inhibitors of RNA- and protein-synthesis, but not by an inhibitor of DNA-synthesis. The increased cytotoxicity of Biostim-treated cells could not be explained by an increased proportion of lymphocytes binding to the target cells (K562). This indicates that Biostim acts by increasing the lytic activity of lymphocytes rather than by increasing the expression of target cell recognition structures. Further, it was shown that culture supernatants of Biostim-exposed monocytes, but not purified lymphocytes, contain factors that augment cytotoxicity of purified lymphocytes. This finding is in line with the previously reported monocyte-dependence of Biostim-induced augmentation of lymphocyte cytotoxicity. Interleukin-2 (IL-2) activity was not observed in supernatants of Biostim-exposed lymphoid cells and augmentation of lymphocyte cytotoxicity could not be inhibited by antibodies directed against interferon (IFN) alpha or gamma. This indicates that Biostim stimulates monocytes to liberate factors other than IL-2 or IFN which augment spontaneous cytotoxicity of lymphocytes.