Talmadge J E
Department of Microbiology and Pathology, University of Nebraska Medical Center, Omaha 68198-3135.
Int J Immunopharmacol. 1992 Apr;14(3):383-90. doi: 10.1016/0192-0561(92)90168-k.
Synergistic therapeutic activity has been observed both preclinically and clinically with combinations of chemotherapeutic and immunotherapeutic agents as well as with several combinations of immunotherapeutic agents. Frequently the synergistic therapeutic activity has been accompanied by unexpected toxicities demonstrating the need for the development of systematic studies to determine the nature and origin of the toxicity observed when these potent immunoregulatory agents are combined. Several examples have been demonstrated including IFN-gamma and TNF and AZT and IFN-alpha. In this paper approaches to study the pathobiology of combination cytokine therapy and strategies to limit the toxicity, to understand its mechanism, and to retain the synergistic therapeutic activity are discussed.
在临床前和临床研究中均观察到，化疗药物与免疫治疗药物联合使用以及多种免疫治疗药物联合使用时具有协同治疗活性。协同治疗活性常常伴随着意外的毒性反应，这表明需要开展系统性研究，以确定这些强效免疫调节药物联合使用时所观察到的毒性的性质和来源。已经有几个例子得到证实，包括干扰素-γ和肿瘤坏死因子以及叠氮胸苷和干扰素-α。本文讨论了研究细胞因子联合治疗病理生物学的方法，以及限制毒性、理解其机制并保留协同治疗活性的策略。
