Correlation between in vitro and systemic effects of native and recombinant interferons-alpha on human natural killer cell cytotoxicity.

The relationship between interferon (IFN) stimulation of natural killer (NK) cell cytotoxicity in vitro and changes in NK cell cytotoxicity resulting from systemic IFN administration was examined in 15 cancer patients in two clinical trials. Ficoll-Hypaque-separated peripheral mononuclear cells (PMC) were incubated 18-20 h with or without IFN on 2 different days prior to therapy initiation to determine in vitro responsiveness to IFN and unstimulated basal levels of NK cell activity, respectively. Three different preparations of IFN-alpha were tested, including native Cantell IFN-alpha and two recombinant DNA-generated species, IFN-r alpha A and IFN-r alpha D. Twenty-four hours after i.m. injection of IFNs, significant NK cell activity enhancement occurred (p = 0.003). The relative extent of cytotoxicity elevation in individual patients resulting from injection significantly correlated (p less than 0.01) with the degree of NK cell activity enhancement induced in vitro by treatment of PMC with the same IFN preparation. These results suggest that patients exhibited individual differences in acute responsiveness to systemic IFN administration, which could be predicted to a certain extent by in vitro testing prior to therapy.