TY - JOUR
T1 - A direct comparison of biological response modulation and clinical side effects by interferon-beta(ser), interferon-gamma, or the combination of interferons beta(ser) and gamma in humans
AU - Schiller, Joan H.
AU - Storer, Barry
AU - Paulnock, Donna M.
AU - Brown, Raymond R.
AU - Datta, Surinder P.
AU - Witt, Patricia L.
AU - Borden, Ernest C.
PY - 1990
Y1 - 1990
N2 - 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.
AB - 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.
KW - biological response modification
KW - clinical cancer trial
KW - interferon
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U2 - 10.1172/JCI114827
DO - 10.1172/JCI114827
M3 - Article
C2 - 2120284
AN - SCOPUS:0025089115
VL - 86
SP - 1211
EP - 1221
JO - Journal of Clinical Investigation
JF - Journal of Clinical Investigation
SN - 0021-9738
IS - 4
ER -