Reddy Pavan
Department of Internal Medicine, University of Michigan Comprehensive Cancer Center, Ann Arbor, Michigan 48109-0942, USA.
Curr Opin Hematol. 2004 Nov;11(6):405-10. doi: 10.1097/01.moh.0000141926.95319.42.
Interleukin-18 (IL-18) has potent immunomodulatory effects. It is the only cytokine with a unique capacity to induce T helper 1 or T helper 2 polarization, depending on the immunologic context. Serum levels of IL-18 are increased in many human diseases and it has been implicated in the pathogenesis of several immune-mediated processes. Some of the recent key advances in the immunobiology of IL-18 are discussed in this review.
Recent data from several laboratories have shed light on the structure of IL-18; the signaling cascades that are initiated; and its role on modulating T cells, dendritic cells, and natural killer cell function. Several new reports have expanded and delineated the role of IL-18 in a multitude of diseases, but only recent advances in the role of IL-18 in three disease processes (acute graft-versus-host disease, insulin-dependent diabetes, and sepsis), where it appears to play paradoxic roles are discussed.
Although emerging data shed more light on the complex role of IL-18 in immune reactions, they also pose more questions. Given the pleiotropic, complex, and at times paradoxic effects of IL-18 in various disease processes, better understanding of its immunobiology might lead to the development of IL-18 and/or its antagonists as therapeutic agents against immune-mediated diseases.
白细胞介素-18(IL-18)具有强大的免疫调节作用。它是唯一一种根据免疫背景具有独特能力诱导辅助性T细胞1型或辅助性T细胞2型极化的细胞因子。在许多人类疾病中,IL-18的血清水平会升高,并且它与多种免疫介导过程的发病机制有关。本文综述了IL-18免疫生物学的一些最新关键进展。
来自多个实验室的最新数据揭示了IL-18的结构、启动的信号级联反应及其在调节T细胞、树突状细胞和自然杀伤细胞功能方面的作用。一些新报告扩展并阐述了IL-18在多种疾病中的作用,但本文仅讨论了IL-18在三种疾病过程(急性移植物抗宿主病、胰岛素依赖型糖尿病和脓毒症)中的作用的最新进展,在这些疾病中它似乎发挥着矛盾的作用。
尽管新出现的数据更清楚地揭示了IL-18在免疫反应中的复杂作用,但也提出了更多问题。鉴于IL-18在各种疾病过程中具有多效性、复杂性且有时具有矛盾性的作用,更好地理解其免疫生物学可能会促使开发IL-18和/或其拮抗剂作为针对免疫介导疾病的治疗药物。