The role of interleukin-37 and interleukin-38 in the development and remission of autism spectrum disorder: a comprehensive review of neuroinflammatory mechanisms and potential therapeutic implications.

This review looks at how brain inflammation might contribute to autism. Researchers found that two specific proteins (IL-37 and IL-38) that normally reduce inflammation behave differently in people with autism. These proteins might help explain why some autistic people have increased brain inflammation. The findings suggest these proteins could potentially be used to help diagnose autism or develop new treatments, but more research is needed to understand their exact role.

This comprehensive review examines the role of two anti-inflammatory cytokines, interleukin-37 (IL-37) and interleukin-38 (IL-38), in autism spectrum disorder pathogenesis. The review synthesizes clinical and experimental findings suggesting these cytokines are important modulators of neuroinflammation in ASD. IL-38 appears to reduce brain inflammation by suppressing microglial activation and decreasing pro-inflammatory cytokine release through the IL-38/IL-36R signaling pathway. IL-37 shows consistent upregulation in ASD-associated brain tissues and functions via the IL-37/IL-18Rα/IL-1R8 pathway to inhibit cytokine synthesis, alter microglial function, and affect gut-brain communication.

Both cytokines represent potential biomarkers for ASD diagnosis and therapeutic targets, though research remains in early stages.

The identification of IL-37 and IL-38 as modulators of neuroinflammation in ASD opens new avenues for biomarker development and therapeutic intervention. However, translation to clinical practice requires further research to validate these findings and establish safety profiles for potential treatments targeting these cytokine pathways.

This is a review study that consolidates existing research rather than presenting new data. The authors note that investigations into IL-37 and IL-38 in ASD are still emerging, indicating limited primary research. No specific sample sizes or methodological details are provided for the underlying studies reviewed.

Autism spectrum disorder (ASD) is a complicated neurodevelopmental syndrome characterized by abnormalities in social communication, lack of interests, and repetitive behaviors. Increasing evidence from recent studies indicates that neuroinflammation and immunological dysregulation play essential roles in the pathogenesis of ASD. This review consolidates current knowledge on two anti-inflammatory cytokines of the IL-1 family, interleukin-38 (IL-38) and interleukin-37 (IL-37), which have recently emerged as essential modulators of neuroimmune mechanisms in ASD, highlighting their emerging roles in ASD pathogenesis and therapeutic potential. Based on a combination of clinical and experimental findings, IL-38 has been reported to exert anti-inflammatory effects by suppressing microglial activation and reducing the release of pro-inflammatory cytokines.

Consequently, modulation of IL-38/IL-36R signaling axis appears to represent a crucial mechanism regulating neuroinflammation in brain regions relevant to autism. On the other hand, studies indicate that IL-37 exhibits a consistent upregulation in the brain tissues associated with ASD, functioning via IL-37/IL-18Rα/IL-1R8 pathway, where it inhibits cytokine synthesis, alters microglial polarization, and affects communication along the gut-brain axis. While these findings establish IL-38 and IL-37 as possible biomarkers for ASD diagnosis and treatment targets, these investigations are still emerging. This review establishes the foundation for understanding the growing importance of cytokines and highlights the requirement for further research to clarify their roles and to formulate potential treatment approaches for ASD.