Emerging functions and therapeutic targets of IL-38 in central nervous system diseases

CNS Neurosci Ther, 2024 · DOI: 10.1111/cns.14550 · Published: January 1, 2024

Simple Explanation

Interleukin (IL)-38 is a cytokine that binds to receptors in the central nervous system (CNS). Research suggests IL-38 is abnormally expressed in patients with ischemic stroke and autism spectrum disorder, indicating it may play a role in neurological diseases. IL-38 can alleviate neuromyelitis optica disorder (NMOD) by inhibiting Th17 expression. It improves ischemic stroke (IS) by protecting against atherosclerosis via regulating immune cells and inflammation. IL-38 mRNA is increased in phagocytes in spinal cord injury (SCI). IL-38 ablation attenuated SCI by reducing immune cell infiltration. The effect and mechanism of IL-38 in CNS diseases remain inadequately characterized.

Study Duration

Not specified

Participants

Not specified

Evidence Level

Review

Key Findings

1
IL-38 alleviates neuromyelitis optica disorder (NMOD) by inhibiting Th17 expression.
2
IL-38 improves ischemic stroke (IS) by protecting against atherosclerosis via regulating immune cells and inflammation.
3
IL-38 reduces IL-1β and CXCL8 release through inhibiting human microglial activity post-ASD.

Research Summary

Interleukin (IL)-38 is a newly discovered cytokine of the IL-1 family, which binds various receptors (i.e., IL-36R, IL-1 receptor accessory protein-like 1, and IL-1R1) in the central nervous system (CNS). Emerging research has shown that IL-38 is abnormally expressed in the serum and brain tissue of patients with ischemic stroke (IS) and autism spectrum disorder (ASD), suggesting that IL-38 may play an important role in neurological diseases. In this review, we summarize the biological characteristics, pathophysiological role, and potential mechanisms of IL-38 in CNS diseases (e.g., NMOD, Alzheimer's disease, ASD, IS, TBI, and SCI), aiming to explore the therapeutic potential of IL-38 in the prevention and treatment of CNS diseases.

Practical Implications

Therapeutic Potential in CNS Diseases

IL-38 represents a promising therapeutic target for CNS diseases, including NMOD, AD, ASD, IS, TBI, and SCI, due to its anti-inflammatory properties.

Diagnostic Biomarker

Serum IL-38 levels may serve as a biomarker for the early diagnosis, treatment monitoring, and prognostic assessment of various diseases, including ischemic stroke and hepatitis B.

Modulation of Inflammatory Pathways

Selective agonists and inhibitors of IL-38, as well as upstream signaling pathways, require further exploration to fully realize its clinical therapeutic and diagnostic value.

Study Limitations

1
The effect and underlying mechanism of IL-38 in CNS diseases remain inadequately characterized.
2
The specific cleavage enzyme for the truncated form of IL-38 and the corresponding cleavage site are still unclear.
3
Clinical applications of IL-38 have not yet been reported.

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