Department of Periodontology, Tufts University School of Dental Medicine, Boston, MA, USA.
Center for Clinical and Translational Research, Forsyth Institute, Cambridge, MA, USA.
J Dent Res. 2020 Dec;99(13):1425-1434. doi: 10.1177/0022034520945209. Epub 2020 Aug 6.
Periodontitis is a complex, multifactorial chronic disease involving continuous interactions among bacteria, host immune/inflammatory responses, and modifying genetic and environmental factors. More than any other cytokine family, the interleukin (IL)-1 family includes key signaling molecules that trigger and perpetuate periodontal inflammation. Over the years, the IL-1 family expanded to include 11 members of cytokines, some with agonist activity (IL-1α, IL-1β, IL-18, IL-33, IL-36α, IL-36β, and IL-36γ), receptor antagonists (IL-1Ra, IL-36Ra), and 2 anti-inflammatory cytokines (IL-37, IL-38). The IL-1 receptor antagonist (IL-1Ra) has emerged as a pivotal player in the defense against periodontitis. IL-33 primarily induces the production of Th2-associated cytokines but acts as an "alarmin" via stimulation of mast cells. The IL-36 subclass of cytokines may be important in regulating mucosal inflammation and homeostasis. IL-37 suppresses innate and acquired immune responses. IL-38 is the most recent member of the IL-1 superfamily and has anti-inflammatory properties similar to those of IL-37 but through different receptors. However, limited evidence exists regarding the role of IL-37 and IL-38 in periodontitis. Despite the development of IL-1 blocking agents, therapeutic blockade of select IL-1 family members for periodontitis has only been partially investigated in preclinical and clinical research, while the development of IL-37 and IL-38 as novel anti-inflammatory drugs has not been considered adequately. Here, we review the key properties of the IL-1 family members and provide insights into targeting or promoting select cytokines as new therapeutic agents.
牙周炎是一种复杂的、多因素的慢性疾病，涉及细菌、宿主免疫/炎症反应以及修饰的遗传和环境因素之间的持续相互作用。在所有细胞因子家族中，白细胞介素 (IL)-1 家族包括触发和持续牙周炎症的关键信号分子。多年来，IL-1 家族不断扩大，包括细胞因子的 11 个成员，其中一些具有激动剂活性（IL-1α、IL-1β、IL-18、IL-33、IL-36α、IL-36β 和 IL-36γ）、受体拮抗剂（IL-1Ra、IL-36Ra）和 2 种抗炎细胞因子（IL-37、IL-38）。IL-1 受体拮抗剂 (IL-1Ra) 已成为防御牙周炎的关键因素。IL-33 主要诱导 Th2 相关细胞因子的产生，但通过刺激肥大细胞充当“警报素”。细胞因子的 IL-36 亚类可能在调节黏膜炎症和稳态中发挥重要作用。IL-37 抑制先天和获得性免疫反应。IL-38 是 IL-1 超家族的最新成员，具有与 IL-37 相似的抗炎特性，但通过不同的受体。然而，关于 IL-37 和 IL-38 在牙周炎中的作用的证据有限。尽管开发了 IL-1 阻断剂，但针对牙周炎的选择性 IL-1 家族成员的治疗性阻断仅在临床前和临床研究中进行了部分研究，而 IL-37 和 IL-38 作为新型抗炎药物的开发尚未得到充分考虑。在这里，我们回顾了 IL-1 家族成员的关键特性，并深入了解了作为新型治疗剂靶向或促进选择性细胞因子的方法。
