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Melatonin has a myriad of immune functions, and we hypothesised that this therapeutic agent could modulate the innate immune system in this cohort.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We investigated neutrophil and monocyte function (CD11b, TLR4 expression by flow cytometry), genes involved in TLR signalling (MyD88, IRAK4, TRIF), the inflammasome (NLRP3, IL-1\u03b2), and circadian rhythm (BMAL, CLOCK, CRY) by qPCR, and inflammatory cytokines (IL-2, IL-6, IL-8, IL-18, IL-1\u03b2, TNF-\u03b1, IFN-\u03b3, IL-10, IL-1ra, VEGF, Epo, GM-CSF) by enzyme-linked immunosorbent assay (ELISA) following immunomodulation with LPS endotoxin and melatonin. 47 children with DS and 23 age- and sex-matched controls were recruited.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We demonstrated that melatonin has several significant effects by reducing CD11b and TLR4 expression, attenuating TLR signalling, genes involved in the inflammasome and has the potential to reduce LPS-induced inflammatory responses.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Immunomodulatory effects of melatonin were found in both paediatric cohorts with more marked effects in the children with DS. Melatonin mediates immune response through a wide array of mechanisms and this immunomodulator may buffer the inflammatory response by regulating pro and anti-inflammatory signalling.<\/jats:p><\/jats:sec><jats:sec><jats:title>Impact<\/jats:title><jats:p><jats:list list-type=\"bullet\"><jats:list-item><jats:p>We highlight that melatonin mediates its immune response through a wide array of mechanisms, its effects appear to be dose dependant and children with Down syndrome may be more receptive to treatment with it.<\/jats:p><\/jats:list-item><jats:list-item><jats:p>Immunomodulatory effects of melatonin were demonstrated with marked effects in the children with Down syndrome with a reduction of MyD88, IL-1\u00df and NLRP3 expression in whole-blood samples.<\/jats:p><\/jats:list-item><jats:list-item><jats:p>Melatonin is a proposed anti-inflammatory agent with a well-established safety profile, that has the potential for mitigation of pro- and anti-inflammatory cytokines in paediatric Down syndrome cohorts, though further clinical trials are warranted.<\/jats:p><\/jats:list-item><\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1038\/s41390-021-01611-6","type":"journal-article","created":{"date-parts":[[2021,8,16]],"date-time":"2021-08-16T12:03:47Z","timestamp":1629115427000},"page":"1812-1820","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Melatonin as an immunomodulator in children with Down syndrome"],"prefix":"10.1038","volume":"91","author":[{"given":"Dean","family":"Huggard","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lynne","family":"Kelly","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy","family":"Worrall","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleanor","family":"Gallagher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lida","family":"Fallah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucas Lu","family":"Yoo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fiona","family":"McGrane","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niamh","family":"Lagan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edna","family":"Roche","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanne","family":"Balfe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Derek G.","family":"Doherty","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleanor J.","family":"Molloy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,8,16]]},"reference":[{"key":"1611_CR1","doi-asserted-by":"publisher","first-page":"1008","DOI":"10.1002\/bdra.20735","volume":"88","author":"SE Parker","year":"2010","unstructured":"Parker, S. 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