Gately M K, Gubler U, Brunda M J, Nadeau R R, Anderson T D, Lipman J M, Sarmiento U
Department of Inflammation/Autoimmune Diseases, Hoffmann-La Roche Inc., Nutley, NJ 07110, USA.
Ther Immunol. 1994 Jun;1(3):187-96.
IL-12 is a cytokine that promotes cell-mediated immunity by promoting Th1-type cytokine responses, enhancing the lytic activity of NK/LAK cells, augmenting specific CTL responses, and inducing the production of IFN-gamma. On the other hand, IL-12 suppresses the development of Th2-type cytokine responses and humoral immunity, particularly IgGl and IgE responses. It is likely that IL-12 normally plays an important role in the host defense against intracellular microbial pathogens. In addition, the administration of rIL-12 to mice has been shown to have potent therapeutic effects in several tumour and infectious disease models. IL-12 has been shown to be more efficacious than IL-2 in several murine tumour models, and toxicology studies suggest that it may have a substantially better therapeutic index. In addition, the long serum half-life of IL-12 relative to other cytokines will allow more flexibility in dosing schedules. However, future clinical trials are required to determine whether the efficacy of IL-12 seen in these experimental models is predictive for its use as an immunomodulatory drug in humans.
白细胞介素-12是一种细胞因子,它通过促进Th1型细胞因子反应、增强自然杀伤细胞/淋巴因子激活的杀伤细胞(NK/LAK细胞)的溶解活性、增强特异性细胞毒性T淋巴细胞(CTL)反应以及诱导γ干扰素(IFN-γ)的产生来促进细胞介导的免疫。另一方面,白细胞介素-12抑制Th2型细胞因子反应和体液免疫的发展,尤其是抑制IgG1和IgE反应。白细胞介素-12可能在宿主抵御细胞内微生物病原体的防御中正常发挥重要作用。此外,已证明给小鼠注射重组白细胞介素-12(rIL-12)在几种肿瘤和传染病模型中具有强大的治疗效果。在几种小鼠肿瘤模型中,白细胞介素-12已被证明比白细胞介素-2更有效,毒理学研究表明它可能具有更好得多的治疗指数。此外,相对于其他细胞因子,白细胞介素-12的血清半衰期较长,这将在给药方案上提供更大的灵活性。然而,需要未来的临床试验来确定在这些实验模型中看到的白细胞介素-12的疗效是否能预测其作为人类免疫调节药物的用途。