Increased spontaneous release of tumour necrosis factor-alpha by alveolar macrophages from wheezy infants.
We determined if alveolar macrophages (AMs) from infants with severe recurrent wheezing episodes release increased amounts of tumour necrosis factor-alpha (TNF-alpha), as described in adults with asthma. We compared TNF-alpha release by unstimulated and lipopolysaccharide-stimulated AMs obtained by bronchoalveolar lavage in 13 wheezy and seven nonwheezy infants (aged 6-36 months) and analysed its regulation by dexamethasone. Metabolites in cell supernatants were quantified by enzyme-linked immunosorbent assay (ELISA) (TNF-alpha) or radioimmunoassay (thromboxane B2 and prostaglandin E2). Comparison of results was performed by the Mann-Whitney U-test and values were expressed as median (interquartile range) in ng x 10(6) cells(-1). Resting AMs from wheezy infants released larger amounts of TNF-alpha and thromboxane B2 as compared to controls: 2.67 (0.89-8.33) vs 0.48 (0.25-1.08) and 75.63 (38.07-158.91) vs 10.03 (7.36-76.08), respectively (p<0.05). When stimulated overnight with bacterial lipopolysaccharide, AMs from both groups released similar amounts of metabolites. Dexamethasone induced a consistent inhibition of the lipopolysaccharide-stimulated release of all the mediators. Our results show that alveolar macrophages from wheezy infants are activated to release increased amounts of tumour necrosis factor-alpha, as in asthma, and suggest that infants with recurrent wheezing may eventually benefit from treatment with glucocorticoids.
Azevedo
I
I
Unité de Pharmacologie Cellulaire, Unité Associée Institut Pasteur-INSERM U-285, Paris, France.
de Blic
J
J
Dumarey
C H
CH
Scheinmann
P
P
Vargaftig
B B
BB
Bachelet
M
M
D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D001999:Bronchoscopy; D002675:Child, Preschool; D003907:Dexamethasone / Q000494:pharmacology; D015232:Dinoprostone / Q000037:antagonists & inhibitors / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology; D006801:Humans; D007223:Infant; D008070:Lipopolysaccharides / Q000494:pharmacology; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D012008:Recurrence; D012016:Reference Values; D012135:Respiratory Sounds / Q000502:physiology*; D013929:Thromboxane B2 / Q000037:antagonists & inhibitors / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000378:metabolism*
D005938:Glucocorticoids; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D013929:Thromboxane B2; D003907:Dexamethasone; D015232:Dinoprostone