title: Omega-3 fatty acids modulate neonatal cytokine response to endotoxin.
abstract: Neonatal immune response is characterized by an uncompensated pro-inflammatory response that can lead to inflammation-related morbidity and increased susceptibility to infection. We investigated the effects of long-chain n-3 polyunsaturated fatty acids (n-3 PUFAs) docosahexaenoic acid (DHA) or eicosapentaenoic acid (EPA) pre-treatment on cytokine secretion to low-concentration endotoxin (lipopolysaccharide, LPS) in THP-1 monocytes and neonatal cord blood (CB) from healthy full-term infants. Pre-treatment of THP-1 cells, with either n-3 PUFA at 25 or 100 μM significantly reduced IL-6, IL-10, and IL-12 secretion while DHA, but not EPA, reduced TNF-α response to LPS. DHA inhibition was stronger compared to EPA and effective at the low concentration. The same concentrations of n-3 PUFAs inhibited IL-12 but not IL-10 cytokine response in whole CB from 9 infants pre-treated for 24 h. To assess clinical relevance for acute response to LPS, the effects of low-concentration DHA at 25 μM or 12.5 μM were assessed before and after LPS exposure of isolated CB mononuclear cells from 20 infants for 1 h. When added before or after LPS, physiologic DHA treatment produced significant concentration-dependent inhibition of TNF-α, IL-6, IL-1β, and IL-8 secretion. The results demonstrate prophylactic and therapeutic modulation of neonatal cytokine response to LPS and provide proof-of-concept that low-concentration administration of n-3 PUFA could attenuate or resolve neonatal inflammatory response.
authors.forename: Michael M
authors.initials: MM
authors.lastname: Espiritu
authors.forename: Hong
authors.initials: H
authors.lastname: Lin
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Foley
authors.forename: Valerie
authors.initials: V
authors.lastname: Tsang
authors.forename: Eunice
authors.initials: E
authors.lastname: Rhee
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Perlman
authors.forename: Susanna
authors.initials: S
authors.lastname: Cunningham-Rundles
mesh_terms: D015415:Biomarkers / Q000097:blood; D002478:Cells, Cultured; D016207:Cytokines / Q000097:blood*; D004281:Docosahexaenoic Acids / Q000008:administration & dosage / Q000494:pharmacology*; D015118:Eicosapentaenoic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D005312:Fetal Blood / Q000378:metabolism*; D006801:Humans; D007231:Infant, Newborn; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000378:metabolism; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000494:pharmacology*; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism
chemical_list: D015415:Biomarkers; D016207:Cytokines; D008070:Lipopolysaccharides; C440499:lipopolysaccharide, Escherichia coli O111 B4; D004281:Docosahexaenoic Acids; D015118:Eicosapentaenoic Acid