Editorial: Cytokines and CNS diseases

The role of cytokines in the central nervous system (CNS) and neurological diseases remains understudied. Nevertheless, numerous studies have demonstrated that cytokines are important in the regulation of CNS homeostasis, neuronal development and synaptogenesis and they are intimately involved in the pathogenesis of epilepsy, autoimmune and neurodegenerative disorders (3,4). Resident glial cells emerged as a potent source of cytokines modulating local microenvironment, synaptic transmission and neuronal function. The evidence that locally produced cytokines can play an immunoregulatory role in CNS inflammation led to reinterpretation of the immune privilege concept of the CNS and the outside-in inflammatory hypothesis of CNS autoimmunity. Theoretically, the hypothesis of neuroimmune network founded by pleotropic cytokines signaling, allows for a more dynamic interpretation of neuroinflammation as well as for identification of cytokine-based therapeutic targets. Introduction of interferon-beta and anti-interleukin 6 (IL-6) or anti-tumor necrosis factor-alpha (TNF-α) therapies in clinical practice advanced the field of autoimmune neurology and provided a direct support for the critical involvement of cytokines in CNS diseases (5).The present collection contains publications that are focused on novel and clinically relevant aspects of the cytokine role in CNS diseases. Grebencicova and Vanhaerents review the normal physiological role of IL-6, and its involvement in neuroinflammatory, autoimmune and SARS-CoV2 -associated disorders, and discuss the clinical utility of anti-IL-6 therapies (6). Basnyat and colleagues report on a positive association between IL-6 plasma levels and antiglutamic acid decarboxylase antibodies in patients with autoimmune epilepsies, providing additional evidence for the involvement of this cytokine in this type of disorders and the therapeutic significance of IL-6 targeting. Caldito provides a broad review on the role of TNF-α in neuroinflammation and neuromodulation and highlights the differential role of its receptors in demyelinating disorders, and the paradoxical effects of anti-TNF-α therapies (8). Abbaoui and colleagues discuss the role of meningeal T cells in neurodegenerative disorders and effect of T cells cytokines in modulating neuronal function and behavior (9). Finally, Giraldo and colleagues report on the immunoregulatory role of granulocyte-colony stimulating factor (G-CSF) that was successfully used in the setting of co-existent autoimmune disorder and immunodeficiency. This collection in our opinion, though not comprehensive and limited in its scope, does highlight the important topics in field of cytokine in CNS diseases and the directions of future research explorations