A DIRECT COMPARISON OF BIOLOGICAL RESPONSE MODULATION AND CLINICAL SIDE-EFFECTS BY INTERFERON-BETA-SER, INTERFERON-GAMMA, OR THE COMBINATION OF INTERFERON-BETA-SER AND INTERFERON-GAMMA IN HUMANS

To directly compare clinical side effects and biological response modification, IFN-β(ser), IFN-γ, or the combination of IFN-β(ser) plus IFN-γ was administered to 21 cancer patients. Each IFN or the combination was given intravenously on days 1, 8, and 15 in varied order. Each IFN and the combination resulted in significant (P < 0.05) modulation of IFN-induced proteins. IFN-β(ser) was more effective than IFN-γ in enhancing 2-5A synthetase activity (P = 0.001). IFN-γ was more effective than IFN-β(ser) in enhancing serum β2 microglobulin expression (P = 0.05) and indoleamine dioxygenase activity, as assessed by decreased serum tryptophan (P = 0.03). The combination enhanced tryptophan catabolism more effectively than IFN-β(ser) in a dose-dependent manner (P < 0.03). IFN-β(ser)/IFN-γ did not potentiate natural killer cells or antibody-dependent cellular toxicity (ADCC). IFN-β(ser)/IFN-γ enhanced monocyte guanylate cyclase activity, as assessed by serum neopterin, more effectively than IFN-γ alone (P = 0.005). Both IFNs and the combination resulted in increases in HLA class II expression on monocytes. However, no significant difference in the level of induction of HLA DQ and HLA DR expression between IFN-β(ser)/IFN-γ IFN-γ and either IFN-β(ser) or IFN-γ was noted. Although frequency and servity of side effects of IFN-β(ser), IFN-γ, or the combination were dose related, induction of induced proteins (with exception of influences on tryptophan catabolism) were not a function of dose administered over the 10-fold range. Continued treatment with the combination intravenously three times a week for 4 wk sustained but did not further potentiate, most of the changes in interferon-induced proteins. Thus, IFN-β(ser) and IFN-γ each resulted in effective and essentially equivalent patterns of induction of induced proteins. When combined, however, these IFNs did not result in potentiation of biological response modification in vivo.