PMID- 30390640 OWN - NLM STAT- MEDLINE DCOM- 20190711 LR - 20190711 IS - 1471-2172 (Electronic) IS - 1471-2172 (Linking) VI - 19 IP - 1 DP - 2018 Nov 3 TI - Altered endotoxin responsiveness in healthy children with Down syndrome. PG - 31 LID - 10.1186/s12865-018-0270-z [doi] LID - 31 AB - BACKGROUND: Down syndrome (DS) is the most common syndromic immunodeficiency with an increased risk of infection, mortality from sepsis, and autoinflammation. Innate immune function is altered in DS and therefore we examined responses in CD11b and Toll like receptor 4 (TLR-4), which are important immune cell surface markers upregulated in response to Lipopolysaccharide (LPS) endotoxin, and the immunomodulator melatonin. Neutrophil and monocyte responses to LPS and melatonin in children with Down syndrome (DS) who were clinically stable were compared to age-matched controls. Whole blood was incubated with LPS and melatonin and the relative expression of CD11b and TLR-4 evaluated by flow cytometry. RESULTS: Children with DS had an increased response to LPS in neutrophils and intermediate monocytes, while also having elevated TLR-4 expression on non-classical monocytes compared to controls at baseline. Melatonin reduced CD11b expression on neutrophils, total monocytes, both classical and intermediate sub-types, in children with DS and controls. CONCLUSION: Melatonin could represent a useful clinical adjunct in the treatment of sepsis as an immunomodulator. Children with DS had increased LPS responses which may contribute to the more adverse outcomes seen in sepsis. FAU - Huggard, Dean AU - Huggard D AUID- ORCID: 0000-0002-0170-8399 AD - Paediatrics, Trinity College, the University of Dublin, Dublin, Ireland. dean.huggard@gmail.com. AD - Trinity Translational Medicine Institute (TTMI), Trinity College Dublin, Dublin, Ireland. dean.huggard@gmail.com. AD - Paediatrics, Tallaght Hospital, Dublin, Ireland. dean.huggard@gmail.com. AD - National Children's Research Centre, Our Lady's Children's Hospital, Crumlin, Dublin, Ireland. dean.huggard@gmail.com. AD - Department of Paediatrics, Trinity Centre for Health Sciences, Tallaght Hospital, Dublin, 24, Ireland. dean.huggard@gmail.com. FAU - McGrane, Fiona AU - McGrane F AD - Paediatrics, Trinity College, the University of Dublin, Dublin, Ireland. AD - Paediatrics, Tallaght Hospital, Dublin, Ireland. FAU - Lagan, Niamh AU - Lagan N AD - Paediatrics, Trinity College, the University of Dublin, Dublin, Ireland. AD - Paediatrics, Tallaght Hospital, Dublin, Ireland. FAU - Roche, Edna AU - Roche E AD - Paediatrics, Trinity College, the University of Dublin, Dublin, Ireland. AD - Paediatrics, Tallaght Hospital, Dublin, Ireland. FAU - Balfe, Joanne AU - Balfe J AD - Paediatrics, Trinity College, the University of Dublin, Dublin, Ireland. AD - Paediatrics, Tallaght Hospital, Dublin, Ireland. FAU - Leahy, Timothy Ronan AU - Leahy TR AD - Paediatrics, Trinity College, the University of Dublin, Dublin, Ireland. AD - Immunology, Our Lady's Children's Hospital, Crumlin, Dublin, Ireland. FAU - Franklin, Orla AU - Franklin O AD - Paediatrics, Trinity College, the University of Dublin, Dublin, Ireland. AD - Cardiology, Our Lady's Children's Hospital, Crumlin, Dublin, Ireland. FAU - Moreno, Ana AU - Moreno A AD - Paediatrics, Trinity College, the University of Dublin, Dublin, Ireland. AD - Trinity Translational Medicine Institute (TTMI), Trinity College Dublin, Dublin, Ireland. FAU - Melo, Ashanty M AU - Melo AM AD - Paediatrics, Trinity College, the University of Dublin, Dublin, Ireland. AD - Trinity Translational Medicine Institute (TTMI), Trinity College Dublin, Dublin, Ireland. FAU - Doherty, Derek G AU - Doherty DG AD - Paediatrics, Trinity College, the University of Dublin, Dublin, Ireland. AD - Trinity Translational Medicine Institute (TTMI), Trinity College Dublin, Dublin, Ireland. FAU - Molloy, Eleanor J AU - Molloy EJ AD - Paediatrics, Trinity College, the University of Dublin, Dublin, Ireland. AD - Trinity Translational Medicine Institute (TTMI), Trinity College Dublin, Dublin, Ireland. AD - Paediatrics, Tallaght Hospital, Dublin, Ireland. AD - Coombe Women and Infants University Hospital, Dublin, Ireland. AD - Neonatology, Our Lady's Children's Hospital, Crumlin, Dublin, Ireland. AD - National Children's Research Centre, Our Lady's Children's Hospital, Crumlin, Dublin, Ireland. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20181103 PL - England TA - BMC Immunol JT - BMC immunology JID - 100966980 RN - 0 (CD11b Antigen) RN - 0 (ITGAM protein, human) RN - 0 (Immunologic Factors) RN - 0 (Lipopolysaccharides) RN - 0 (TLR4 protein, human) RN - 0 (Toll-Like Receptor 4) RN - JL5DK93RCL (Melatonin) SB - IM MH - CD11b Antigen/*blood MH - Child MH - Child, Preschool MH - Down Syndrome/*immunology MH - Escherichia coli/immunology MH - Female MH - Humans MH - Immunologic Factors/therapeutic use MH - Immunomodulation MH - Lipopolysaccharides/*immunology MH - Male MH - Melatonin/*immunology/therapeutic use MH - Monocytes/immunology MH - Neutrophils/immunology MH - Sepsis/immunology/mortality/therapy MH - Toll-Like Receptor 4/*blood PMC - PMC6215672 OTO - NOTNLM OT - Down syndrome OT - Endotoxin OT - Immunomodulation OT - Inflammation OT - Innate immunity COIS- ETHICS APPROVAL AND CONSENT TO PARTICIPATE: Our research involved whole blood samples from paediatric patients. Ethical approval was received in advance by the research and ethics committees from Our lady's children's hospital Crumlin (Ref: GEN 565/17), and the SJH.AMNCH ethics committee (Ref: 2017-05). Approval Letters available on request. All participant's parents received an information leaflet and full written consent was obtained prior to enrolment in the study. CONSENT FOR PUBLICATION: N/A COMPETING INTERESTS: The authors declare that they have no competing interests. PUBLISHER'S NOTE: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. EDAT- 2018/11/06 06:00 MHDA- 2019/07/12 06:00 PMCR- 2018/11/03 CRDT- 2018/11/05 06:00 PHST- 2018/08/21 00:00 [received] PHST- 2018/10/18 00:00 [accepted] PHST- 2018/11/05 06:00 [entrez] PHST- 2018/11/06 06:00 [pubmed] PHST- 2019/07/12 06:00 [medline] PHST- 2018/11/03 00:00 [pmc-release] AID - 10.1186/s12865-018-0270-z [pii] AID - 270 [pii] AID - 10.1186/s12865-018-0270-z [doi] PST - epublish SO - BMC Immunol. 2018 Nov 3;19(1):31. doi: 10.1186/s12865-018-0270-z.