Interleukin-10 Production after Pro-Inflammatory Stimulation of Neutrophils and Monocytic Cells of the Newborn

Autor: Denise C Clark, Veronika Miskolci, Dennis Davidson, Gigliola Dolmaian, Ivana Vancurova
Rok vydání: 2007
Předmět:
Zdroj: Neonatology. 92:127-133
ISSN: 1661-7819
1661-7800
DOI: 10.1159/000101432
Popis: Background: Neutrophils followed by monocytic cells are recruited into the lung during the early development of bronchopulmonary dysplasia (BPD). Objectives: 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.
Databáze: OpenAIRE