Steroids fail to down-regulate respiratory syncytial virus-induced IL-8 secretion in infants.
In the first year of life, respiratory syncytial virus (RSV) is the major cause of bronchiolitis and is characterized by extensive inflammatory cell influx to airways. We investigated whether this might reflect a failure to down-regulate secretion of the chemokine IL-8, which has been identified as a key chemoattractant during host defense to RSV. Two milliliters of blood were obtained from infants, children aged 1-12 y, and adults. Peripheral blood mononuclear cells (PBMC) were isolated and infected with RSV, and IL-8 secretion was measured by ELISA. The effect of preincubation of PBMC with either 0.1-10 micro M dexamethasone or 1-100 ng/mL of one of the down-regulatory T helper 2 cytokines IL-4, IL-10, or IL-13 before RSV infection was examined. RSV stimulated IL-8 secretion in a dose-dependent manner similarly in all age groups. IL-8 secretion occurred mainly within 24 h of infection, with maximal concentrations of 30,000-46,000 pg/10(6) cells. IL-4 caused modest inhibition and IL-10 and IL-13 caused no inhibition of IL-8 secretion in all groups. Dexamethasone inhibited IL-8 secretion by 34 +/- 8% in children and by 41 +/- 3% in adults but had no effect on infant PBMC. In summary, RSV-induced IL-8 secretion from infant PBMC is equal to that in children and adults and relatively unaffected by down-regulatory cytokines. However, the inhibitory effects of steroids on IL-8 secretion are absent in infants, which may partly explain why they develop more severe bronchiolitis, and why steroid therapy is unsuccessful in clinical practice.
Department of Infectious Diseases, Faculty of Medicine, Imperial College of Science, Technology and Medicine, Hammersmith Campus, London, UK.
Lynette H
LH
Thomas
Mike
M
Sharland
Jon S
JS
Friedland
D000328:Adult; D002460:Cell Line; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D003907:Dexamethasone / Q000494:pharmacology* / Q000627:therapeutic use; D015536:Down-Regulation; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D007223:Infant; D016753:Interleukin-10 / Q000494:pharmacology; D018793:Interleukin-13 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D016209:Interleukin-8 / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology* / Q000821:virology*; D008297:Male; D012136:Respiratory Syncytial Viruses / Q000276:immunology* / Q000502:physiology
D005938:Glucocorticoids; D018793:Interleukin-13; D016209:Interleukin-8; D016753:Interleukin-10; D015847:Interleukin-4; D003907:Dexamethasone