Regulation of human natural killer cell cytotoxicity by recombinant leukocyte interferon clone A

We have studied the peripheral blood natural killer (NK) cell cytotoxicity of 32 cancer patients prior to and after single and multiple injections of various doses of human recombinant leukocyte interferon clone A (IFN-alpha rA). Consistent decline in NK-cell cytotoxicity of all cancer patients was observed 4 and 8 h after a single injection of IFN-alpha rA. Twenty-four hours after the injection, NK-cell cytotoxicity of patients with low NK cell phenotype (NK-LR) was significantly augmented, whereas that of most patients with medium (NK-MR) or high (NK-HR) NK phenotype was depressed. After multiple IFN-alpha rA injections, depression of NK-cell cytotoxicity was observed in a number of NK-MR and NK-HR patients, whereas in some patients with NK-LR phenotype, elevated NK-cell levels were observed. No direct correlation between NK-cell augmentation and serum IFN levels was detected. In vitro studies demonstrated that NK-cell cytotoxicity of normal donors was augmented by IFN-alpha rA (10(3) U/ml). Augmentation of NK cells was also observed in cancer patients after in vitro addition of IFN-alpha rA, but only prior to and not after in vivo IFN-alpha rA therapy.