Evidence map›Paper›PMID 34400791›Full record

ArticlePediatric research2022

Melatonin as an immunomodulator in children with Down syndrome.

Dean Huggard, Lynne Kelly, Amy Worrall, Eleanor Gallagher, Lida Fallah, Lucas Lu Yoo, Fiona McGrane, Niamh Lagan, Edna Roche, Joanne Balfe and 2 more

Open access · hybridAbstract read
In one paragraph

Article in Pediatric research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
1.3field-weighted citation impact, top 22% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

9 citing papers in PubMed, 21 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Melatonin supplementation: new insights into health and disease.Sleep & breathing = Schlaf & Atmung · 2025
    Review
  6. Review
  7. Melatonin, an Antitumor Necrosis Factor Therapy.Journal of pineal research · 2025
    Review
  8. Review
  9. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 3 institutions in 1 country.

Dean HuggardPaediatrics, Trinity College, The University of Dublin & Trinity Research in Childhood Centre (TRiCC), Dublin, Ireland. huggardd@tcd.ie.
Lynne KellyPaediatrics, Trinity College, The University of Dublin & Trinity Research in Childhood Centre (TRiCC), Dublin, Ireland.
Amy WorrallPaediatrics, Trinity College, The University of Dublin & Trinity Research in Childhood Centre (TRiCC), Dublin, Ireland.
Eleanor GallagherPaediatrics, Trinity College, The University of Dublin & Trinity Research in Childhood Centre (TRiCC), Dublin, Ireland.
Lida FallahTrinity Translational Medicine Institute (TTMI), St James Hospital, Trinity College Dublin, Dublin, Ireland.
Lucas Lu YooPaediatrics, Trinity College, The University of Dublin & Trinity Research in Childhood Centre (TRiCC), Dublin, Ireland.
Fiona McGranePaediatrics, Children's health Ireland (CHI) at Tallaght, Dublin, Ireland.
Niamh LaganPaediatrics, Trinity College, The University of Dublin & Trinity Research in Childhood Centre (TRiCC), Dublin, Ireland.
Edna RochePaediatrics, Trinity College, The University of Dublin & Trinity Research in Childhood Centre (TRiCC), Dublin, Ireland.
Joanne BalfePaediatrics, Trinity College, The University of Dublin & Trinity Research in Childhood Centre (TRiCC), Dublin, Ireland.
Derek G DohertyPaediatrics, Trinity College, The University of Dublin & Trinity Research in Childhood Centre (TRiCC), Dublin, Ireland.
Eleanor J MolloyPaediatrics, Trinity College, The University of Dublin & Trinity Research in Childhood Centre (TRiCC), Dublin, Ireland.
Trinity College Dublin · IEChildren's Health Ireland at Crumlin · IECoombe Women & Infants University Hospital · IE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundDown syndrome (DS) is a disorder characterised by marked immune dysfunction, increased mortality from sepsis, chronic inflammation, increased oxidative stress, sleep disturbance and possibly abnormal endogenous melatonin levels. Melatonin has a myriad of immune functions, and we hypothesised that this therapeutic agent could modulate the innate immune system in this cohort.

methodsWe investigated neutrophil and monocyte function (CD11b, TLR4 expression by flow cytometry), genes involved in TLR signalling (MyD88, IRAK4, TRIF), the inflammasome (NLRP3, IL-1β), and circadian rhythm (BMAL, CLOCK, CRY) by qPCR, and inflammatory cytokines (IL-2, IL-6, IL-8, IL-18, IL-1β, TNF-α, IFN-γ, 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.

resultsWe 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.

conclusionsImmunomodulatory 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. IMPACT: 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. Immunomodulatory effects of melatonin were demonstrated with marked effects in the children with Down syndrome with a reduction of MyD88, IL-1ß and NLRP3 expression in whole-blood samples. 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.

Indexed as

Down SyndromeMelatoninAnti-Inflammatory AgentsChildCytokinesHumansImmunologic FactorsInflammasomesLipopolysaccharidesMyeloid Differentiation Factor 88NLR Family, Pyrin Domain-Containing 3 ProteinToll-Like Receptor 4Anti-Inflammatory AgentsCytokinesImmunologic FactorsInflammasomesLipopolysaccharidesMelatoninMyeloid Differentiation Factor 88NLR Family, Pyrin Domain-Containing 3 ProteinToll-Like Receptor 4

Identifiers

PMID34400791
PMCPMC9270227
OpenAlexW3193876121

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.