Interleukin-10 production after pro-inflammatory stimulation of neutrophils and monocytic cells of the newborn. Comparison to exogenous interleukin-10 and dexamethasone levels needed to inhibit chemokine release.
BACKGROUND
Neutrophils followed by monocytic cells are recruited into the lung during the early development of bronchopulmonary dysplasia (BPD).


OBJECTIVE
We determined: (1) the capacity of polymorphonuclear leukocytes (PMNs) and peripheral blood monocytic cells (PBMCs) of the newborn to produce and release the anti-inflammatory cytokine, interleukin (IL)-10, after stimulation by lipopolysaccharide (LPS) or tumor necrosis factor (TNF), and (2) the levels of exogenous IL-10 and/or dexamethasone (DEX) needed to inhibit the release of the pro-inflammatory chemokine IL-8 from stimulated cells.


METHODS
PMNs and PBMCs were isolated from cord blood of healthy term infants. RT-PCR and ELISA were used to detect mRNA and cytokine levels from culture media, respectively.


RESULTS
We found that PMNs did not produce IL-10 mRNA or release IL-10 but did produce IL-8 mRNA by 1 h. PBMCs did produce IL-10 mRNA after 4 h (with IL-8 mRNA expression by 1 h). LPS-stimulated PBMCs released IL-10 to a maximum of 1,038 pg/ml/5 million cells (56 femtomolar). Equimolar doses of exogenous IL-10 or DEX produced up to 83% inhibition of IL-8 from PMNs. Exogenous IL-10 was more potent than DEX, on an equimolar basis, with regard to IL-8 release from PBMCs (90 vs. 33% respectively at a 10 nanomolar level). No inhibition of IL-8 release by IL-10 or DEX was observed at 100 femtomolar level. IL-10 and DEX did not have an additive inhibitory effect on IL-8 release.


CONCLUSIONS
We conclude that for the newborn: (1) PBMCs produce IL-10 far below the level needed to inhibit a submaximal release of IL-8 from PMNs or PBMCs, and (2) exogenous IL-10 was equipotent or more potent than therapeutic levels of DEX on inhibition of IL-8 from these cells. Further studies are needed to determine if exogenous IL-10 may be useful in the treatment of BPD or other inflammatory disorders of the newborn.
Davidson
Dennis
D
Division of Neonatal-Perinatal Medicine, Schneider Children's Hospital, North Shore-Long Island Jewish Health System, The Long Island Campus for the Albert Einstein College of Medicine, New Hyde Park, NY 11040, USA. davidson@lij.edu
Miskolci
Veronika
V
Clark
Denise C
DC
Dolmaian
Gigliola
G
Vancurova
Ivana
I
D002478:Cells, Cultured; D002585:Cesarean Section; D003907:Dexamethasone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D017558:Elective Surgical Procedures; D005312:Fetal Blood / Q000166:cytology; D015870:Gene Expression / Q000187:drug effects; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D007231:Infant, Newborn; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D016209:Interleukin-8 / Q000037:antagonists & inhibitors / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D005938:Glucocorticoids; D016209:Interleukin-8; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D003907:Dexamethasone