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.
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.
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直接比较干扰素-β-丝氨酸、干扰素-γ或干扰素-β-丝氨酸和γ-干扰素的组合对人体的生物反应调节和临床副作用。
DOI：
10.1172/jci114827
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发表时间：
1990
期刊：
影响因子：
--
通讯作者：
Borden,EC
中科院分区：
文献类型：
--
作者：
Schiller,JH;Storer,B;Paulnock,DM;Brown,RR;Datta,SP;Witt,PL;Borden,EC
为了直接比较临床副作用和生物反应的改变，对 21 名癌症患者施用了 IFN-β 丝氨酸、IFN-γ 或 IFN-β 丝氨酸加 IFN-γ 的组合。每种 IFN 或组合在第 1、8 和 15 天以不同的顺序静脉注射。每种 IFN 及其组合都会对 IFN 诱导的蛋白质产生显着的调节（P 小于 0.05）。 IFN-β Ser 在增强 2-5A 合成酶活性方面比 IFN-γ 更有效（P = 0.001）。 IFN-γ 在增强血清 β2 微球蛋白表达（P = 0.05）和吲哚胺双加氧酶活性方面比 IFN-β ser 更有效，通过降低血清色氨酸来评估（P = 0.03）。该组合比 IFN-β Ser 更有效地增强色氨酸分解代谢，且呈剂量依赖性（P 小于 0.03）。 IFN-β Ser/IFN-γ 不会增强自然杀伤细胞或抗体依赖性细胞毒性 (ADCC)。通过血清新蝶呤评估，IFN-β Ser/IFN-gamma 比单独使用 IFN-gamma 更有效地增强单核细胞鸟苷酸环化酶活性（P = 0.005）。 IFN 及其组合均导致单核细胞上 HLA II 类表达增加。然而，在IFN-β Ser/IFN-γ与IFN-β Ser或IFN-γ之间，HLA DQ和HLA DR表达的诱导水平没有显着差异。尽管 IFN-β Ser、IFN-γ 或组合的副作用的频率和严重性与剂量相关，但诱导蛋白的诱导（除了对色氨酸分解代谢的影响之外）并不是 10 倍范围内施用剂量的函数。每周静脉注射该组合 3 次，持续 4 周，继续治疗干扰素诱导的蛋白质的大部分变化，但没有进一步增强。因此，IFN-β丝氨酸和IFN-γ各自产生有效且基本相同的诱导蛋白诱导模式。然而，当组合时，这些干扰素并没有导致体内生物反应修饰的增强。
To directly compare clinical side effects and biological response modification, IFN-beta ser, IFN-gamma, or the combination of IFN-beta ser plus IFN-gamma 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 less than 0.05) modulation of IFN-induced proteins. IFN-beta ser was more effective than IFN-gamma in enhancing 2-5A synthetase activity (P = 0.001). IFN-gamma was more effective than IFN-beta ser in enhancing serum beta 2 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-beta ser in a dose-dependent manner (P less than 0.03). IFN-beta ser/IFN-gamma did not potentiate natural killer cells or antibody-dependent cellular toxicity (ADCC). IFN-beta ser/IFN-gamma enhanced monocyte guanylate cyclase activity, as assessed by serum neopterin, more effectively than IFN-gamma 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-beta ser/IFN-gamma and either IFN-beta ser or IFN-gamma was noted. Although frequency and servity of side effects of IFN-beta ser, IFN-gamma, 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-beta ser and IFN-gamma 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.Images