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.