Clinical Use of Interleukin-6 Blockade in Neuroimmunological Disorders

Interleukin-6 (IL-6) is a multifunctional cytokine that plays a critical role in immune regulation, host defense, and tissue repair. Within the central nervous system (CNS), IL-6 contributes to both neuroprotection and neuroinflammation, depending on the signaling pathway involved; classic signaling, trans-signaling, or trans-presentation. Dysregulation of IL-6, particularly through sustained overexpression, disrupts the blood-brain barrier (BBB) integrity, promotes glial activation, and amplifies chronic inflammation, thereby contributing to the pathophysiology of numerous neurological disorders. This review aims to evaluate the role of IL-6 in neuroinflammatory processes and its clinical implications across a spectrum of neurological diseases. It focuses on the therapeutic potential and safety profile of IL-6 inhibitors, particularly tocilizumab and satralizumab. Key conditions discussed include neuromyelitis optica spectrum disorder (NMOSD), myelin oligodendrocyte glycoprotein-associated disease (MOGAD), autoimmune encephalitis (AE), neuro-Behçet's disease (NBD), myasthenia gravis (MG), epilepsy, multiple sclerosis (MS), and Alzheimer's disease (AD). Clinical trials have demonstrated the efficacy of IL-6 receptor blockade in reducing relapse rates in NMOSD, leading to regulatory approvals. Promising off-label results have also been reported in treatment-resistant cases of MOGAD, epilepsy, and autoimmune conditions. However, IL-6 inhibition carries risks such as serious infections and paradoxical inflammatory reactions. Targeting the IL-6 pathway represents a significant advancement in neuroimmunology, offering new therapeutic opportunities for otherwise refractory conditions. Future research should focus on large-scale randomized controlled trials and the development of IL-6 inhibitors capable of crossing the BBB to enhance CNS-specific efficacy. Cost-related accessibility also remains a major challenge for broader clinical application.