Ciolli V, Sestili P, Brigato M, Gabriele L, Varano F, Locardi C, Belardelli F
Laboratorio di Virologia, Istituto Superiore di Sanità, Rome, Italy.
Ann Ist Super Sanita. 1990;26(3-4):441-51.
Cytokines are cellular proteins capable of exerting a variety of different biological effects both in vitro and in vivo. The availability of large amounts of recombinant highly purified cytokines now allows clinicians to explore the possible therapeutic use of these molecules. Some of these cytokines (such as interferons, "tumor necrosis factor" and interleukin-2) have been widely shown to exert antitumor effects in animal model systems and are now used in clinical trials to treat cancer patients. However, the mechanisms of these antitumor effects are poorly understood. In view of their multiple biological properties it appears very important to define suitable experimental systems for studying the antitumor effects of cytokines. In fact, one of the major problems facing researchers involved in the cytokine field is to evaluate the relevance of the different biological effects observed in in vitro cell systems with respect to the antitumor effects observed in vivo. Tumor bearing-mice injected with transplantable tumor cells can represent unique, preclinical, experimental systems to study the mechanisms of antitumor action of cytokines. In fact, only by combining the information derived from in vitro cell systems with data obtained from suitable animal models it is possible to achieve relevant insights on the mechanisms of antitumor action of cytokines. Such in vitro and in vivo studies should represent a basic support for a better use of cytokines in clinical trials with cancer patients. In this article we review the major mouse models for studying the mechanisms of antitumor action of cytokines. Furthermore, we briefly summarize our data on the antitumor effects of cytokines in mice injected with transplantable Friend leukemia cells and we discuss the advantages and the disadvantages in choosing specific animal models for studying the antitumor effects of cytokines.
细胞因子是一类细胞蛋白，在体外和体内均能发挥多种不同的生物学效应。现在有大量重组高纯度细胞因子可供使用，这使得临床医生能够探索这些分子可能的治疗用途。其中一些细胞因子（如干扰素、“肿瘤坏死因子”和白细胞介素-2）已在动物模型系统中广泛显示出抗肿瘤作用，目前正用于治疗癌症患者的临床试验。然而，这些抗肿瘤作用的机制尚不清楚。鉴于它们具有多种生物学特性，确定合适的实验系统来研究细胞因子的抗肿瘤作用显得非常重要。事实上，细胞因子领域的研究人员面临的主要问题之一是评估在体外细胞系统中观察到的不同生物学效应与在体内观察到的抗肿瘤效应之间的相关性。注射可移植肿瘤细胞的荷瘤小鼠可以代表研究细胞因子抗肿瘤作用机制的独特的临床前实验系统。实际上，只有将来自体外细胞系统的信息与从合适的动物模型获得的数据相结合，才有可能深入了解细胞因子的抗肿瘤作用机制。这样的体外和体内研究应该为在癌症患者的临床试验中更好地使用细胞因子提供基本支持。在本文中，我们综述了用于研究细胞因子抗肿瘤作用机制的主要小鼠模型。此外，我们简要总结了我们关于细胞因子对注射可移植弗氏白血病细胞的小鼠的抗肿瘤作用的数据，并讨论了选择特定动物模型来研究细胞因子抗肿瘤作用的优缺点。
