Abstract
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.
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Acknowledgements
This work has received funding from the Swiss National Science Foundation (733 310030_170320, 310030_188450 and CRSII5_183478 to B.B. and 310030_189043 to T.D.), European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement no. 882424 to B.B.), the Agence Nationale pour la Recherche CE17-0014 and ANR-23-CE15-0008 (to R.L.), Fondation pour la Recherche Médicale, ARSEP — French MS society, BETPSY RHU 18- RHUS-0012 (to R.L.).
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Becher, B., Derfuss, T. & Liblau, R. Targeting cytokine networks in neuroinflammatory diseases. Nat Rev Drug Discov 23, 862–879 (2024). https://doi.org/10.1038/s41573-024-01026-y
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DOI: https://doi.org/10.1038/s41573-024-01026-y
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