{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T20:13:42Z","timestamp":1793218422243,"version":"4.5.0"},"reference-count":141,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T00:00:00Z","timestamp":1764892800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006014","name":"College of Medicine and Health Sciences, United Arab Emirates University","doi-asserted-by":"publisher","award":["12R207, 12M099, 12M274"],"award-info":[{"award-number":["12R207, 12M099, 12M274"]}],"id":[{"id":"10.13039\/501100006014","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>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-18R\u03b1\/IL-1R8 pathway, where it inhibits cytokine synthesis, alters microglial polarization, and affects communication along the gut\u2013brain 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.<\/jats:p>","DOI":"10.3389\/fimmu.2025.1716197","type":"journal-article","created":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T06:29:29Z","timestamp":1764916169000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["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"],"prefix":"10.3389","volume":"16","author":[{"given":"Zakeya","family":"Al Rasbi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiba","family":"Orsud","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sumaya Hasan","family":"Zoughbor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malak","family":"Hajar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdulla","family":"Mahboob","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bassem","family":"Sadek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,12,5]]},"reference":[{"key":"B1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.15585\/mmwr.ss6904a1","article-title":"Prevalence of autism spectrum disorder among children aged 8 years\u2014Autism and Developmental Disabilities Monitoring Network, 11 sites, United States, 2016","volume":"69","author":"Maenner","year":"2020","journal-title":"MMWR Surveill Summ"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.3390\/children11111311","article-title":"Autism spectrum disorder in children: early signs and therapeutic interventions","volume":"11","author":"Abualai","year":"2024","journal-title":"Children"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2022.12.001","article-title":"Innate immune dysfunction and neuroinflammation in autism spectrum disorder (ASD)","volume":"108","author":"Hughes","year":"2023","journal-title":"Brain Behav Immun"},{"key":"B4","doi-asserted-by":"crossref","DOI":"10.1016\/j.bbi.2010.08.003","article-title":"Elevated plasma cytokines in autism spectrum disorders provide evidence of immune dysfunction and are associated with impaired behavioral outcome","volume":"25","author":"Ashwood","year":"2011","journal-title":"Brain Behavior Immun"},{"key":"B5","doi-asserted-by":"crossref","DOI":"10.1016\/j.jneuroim.2008.12.002","article-title":"Elevated immune response in the brain of autistic patients","volume":"207","author":"Li","year":"2009","journal-title":"J Neuroimmunol"},{"key":"B6","doi-asserted-by":"crossref","DOI":"10.1038\/npp.2016.158","article-title":"The role of the immune system in autism spectrum disorder","volume":"42","author":"Meltzer","year":"2017","journal-title":"Neuropsychopharmacology"},{"key":"B7","doi-asserted-by":"crossref","DOI":"10.1016\/j.bbi.2011.08.007","article-title":"The role of immune dysfunction in the pathophysiology of autism","volume":"26","author":"Onore","year":"2012","journal-title":"Brain Behavior Immun"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2023.1125428","article-title":"Microglia and astrocytes underlie neuroinflammation and synaptic susceptibility in autism spectrum disorder","volume":"17","author":"Xiong","year":"2023","journal-title":"Front Neurosci"},{"key":"B9","doi-asserted-by":"crossref","DOI":"10.1073\/pnas.2004666117","article-title":"IL-38 inhibits microglial inflammatory mediators and is decreased in amygdala of children with autism spectrum disorder","volume":"117","author":"Tsilioni","year":"2020","journal-title":"Proc Natl Acad Sci U S A"},{"key":"B10","doi-asserted-by":"crossref","first-page":"1272","DOI":"10.3390\/jmse10091272","article-title":"Molecular characterization and expression analysis of novel interleukin-1 family member (nIL-1Fm) gene in Nile Tilapia (Oreochromis niloticus)","volume":"10","author":"Wangkahart","year":"2022","journal-title":"J Mar Sci Eng"},{"key":"B11","first-page":"3","article-title":"A world of wonders: interleukin-1. 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