Institute of experimental Immunology, University of Zurich, Zurich, Switzerland.
Department of Neurology and Biomedicine, Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), University Hospital Basel, University of Basel, Basel, Switzerland.
Nat Rev Drug Discov. 2024 Nov;23(11):862-879. doi: 10.1038/s41573-024-01026-y. Epub 2024 Sep 11.
In neuroinflammatory diseases, systemic (blood-borne) leukocytes invade the central nervous system (CNS) and lead to tissue damage. A causal relationship between neuroinflammatory diseases and dysregulated cytokine networks is well established across several preclinical models. Cytokine dysregulation is also observed as an inadvertent effect of cancer immunotherapy, where it often leads to neuroinflammation. Neuroinflammatory diseases can be separated into those in which a pathogen is at the centre of the immune response and those of largely unknown aetiology. Here, we discuss the pathophysiology, cytokine networks and therapeutic landscape of 'sterile' neuroinflammatory diseases such as multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), neurosarcoidosis and immune effector cell-associated neurotoxicity syndrome (ICANS) triggered by cancer immunotherapy. Despite successes in targeting cytokine networks in preclinical models of neuroinflammation, the clinical translation of targeting cytokines and their receptors has shown mixed and often paradoxical responses.
在神经炎症性疾病中，系统性（血源性）白细胞侵入中枢神经系统（CNS）并导致组织损伤。在几种临床前模型中，神经炎症性疾病与细胞因子网络失调之间存在因果关系已得到充分证实。细胞因子失调也被视为癌症免疫疗法的意外作用，常导致神经炎症。神经炎症性疾病可分为以病原体为中心的免疫反应和病因不明的疾病。在这里，我们讨论了诸如多发性硬化症（MS）、视神经脊髓炎谱系障碍（NMOSD）、神经结节病和免疫效应细胞相关神经毒性综合征（ICANS）等“无菌”神经炎症性疾病的病理生理学、细胞因子网络和治疗前景，这些疾病是由癌症免疫疗法引发的。尽管在神经炎症的临床前模型中靶向细胞因子网络取得了成功，但靶向细胞因子及其受体的临床转化显示出混合的、常常是矛盾的反应。
