Targeting cytokine networks in neuroinflammatory diseases

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. Dysregulated cytokine networks are important in the pathogenesis of neuroinflammation. This Review discusses targeting cytokines and their receptors in non-infectious central nervous system inflammatory diseases such as multiple sclerosis and neurosarcoidosis, as well as in the neurotoxic adverse events that can be triggered by cancer immunotherapy.