Interleukins in Neuroimmunology: Bridging CNS Disorders and Peripheral Inflammation

Trombetta Dewhirst^*
*Correspondence: Trombetta Dewhirst, Department of Immunology, University of California, San Francisco, CA, USA, Email:

Introduction

Neuroimmunology, the interdisciplinary field that explores the interface between the nervous system and immune system, has undergone a dramatic evolution over the past few decades. Once considered an immune-privileged site, the Central Nervous System (CNS) is now recognized as a highly dynamic and immunologically active compartment. It maintains intricate communication with the peripheral immune system through various molecular mediators, among which interleukins play a central role. Interleukins, a diverse group of cytokines primarily involved in immune cell signaling, are increasingly implicated in the pathophysiology of neurological disorders ranging from multiple sclerosis (MS) and Alzheimer's disease (AD) to depression, schizophrenia, and neuropathic pain. These cytokines not only mediate local immune responses within the CNS but also serve as critical messengers between peripheral immune cells and neural tissues. Their dysregulation is associated with both neuroinflammatory and neurodegenerative cascades. Understanding the role of interleukins in bridging peripheral inflammation with CNS pathology offers novel insights into disease mechanisms and therapeutic targets [1].

Description

The CNS and immune system engage in constant surveillance and communication, with interleukins acting as pivotal mediators. Although once believed to be isolated from systemic immune influences, the CNS is now known to express various cytokine receptors and produce interleukins via resident cells such as astrocytes, microglia, endothelial cells, and neurons. Peripheral immune cells also infiltrate the CNS under both physiological and pathological conditions, guided by chemokines and cytokines, thus establishing a bidirectional communication axis. The blood-brain barrier (BBB), though selective, is not impervious and can be modulated by inflammatory cues, allowing interleukin-mediated signaling across the neurovascular unit [2].

Therapeutically, IL-6 blockade with monoclonal antibodies such as tocilizumab has been approved for autoimmune diseases like rheumatoid arthritis and is being investigated for efficacy in MS, neuromyelitis optica spectrum disorder (NMOSD), and even neuropsychiatric lupus. Modulating IL-6 signaling could potentially reduce neuroinflammation and restore neuroimmune balance. IL-17, the signature cytokine of Th17 cells, is a potent proinflammatory molecule implicated in CNS autoimmunity. IL-17A promotes the recruitment of neutrophils, enhances BBB permeability, and activates glial cells to produce chemokines and cytokines that perpetuate inflammation. Th17 cells infiltrate the CNS during neuroinflammatory episodes, particularly in MS and its animal model, experimental autoimmune encephalomyelitis [3].

IL-10 is a potent anti-inflammatory cytokine produced by Tregs, microglia, macrophages, and astrocytes. It suppresses the expression of proinflammatory cytokines, antigen presentation, and glial activation, thereby limiting immune-mediated damage in the CNS. IL-10 signaling promotes neuroprotection, enhances tissue repair, and supports the survival of oligodendrocytes and neurons. In neurodegenerative diseases, IL-10 exerts protective effects by inhibiting microglial overactivation and reducing oxidative stress. In stroke models, IL-10 administration limits infarct size and improves functional outcomes. However, IL-10 levels are often reduced in chronic CNS diseases, suggesting a failure of endogenous regulatory mechanisms. Therapeutic strategies aimed at enhancing IL-10 signaling, either through gene therapy, recombinant cytokines, or induction of IL-10-producing cells, are being explored for neurodegenerative and neuroinflammatory diseases. IL-10â??s role in restoring immune tolerance makes it a promising target for modulating neuroimmune interactions [4,5].

Conclusion

Interleukins serve as vital messengers in the neuroimmune dialogue, bridging peripheral inflammation and CNS disorders. Their roles extend from orchestrating neuroinflammatory responses to facilitating tissue repair and neuronal survival. Dysregulated interleukin signaling underlies a wide spectrum of neurological and psychiatric diseases, making them attractive targets for therapeutic intervention. The evolving understanding of how interleukins modulate glial activation, BBB integrity, neuronal function, and peripheral-CNS communication is reshaping the landscape of neuroimmunology. Future research aimed at precisely modulating interleukin pathways holds the promise of revolutionizing the treatment of CNS disorders and ushering in an era of targeted neuroimmune therapy.

Acknowledgement

None.

Conflict of Interest

None.

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