Inhibition of macrophage proinflammatory cytokine expression by steroids and recombinant IL-10.
Chronic lung disease (CLD) of prematurity is a prolonged respiratory failure in very-low-birth-weight neonates. Proinflammatory cytokines have been implicated in the development of CLD. Steroids have been shown to produce some improvement in neonates with this disease. The purpose of this study was to evaluate the downregulation of these proinflammatory cytokines by dexamethasone, budesonide and recombinant IL-10 (rIL-10) in order to elucidate the mechanism of the clinical benefit of steroids in babies. Our results showed that dexamethasone, budesonide and rIL-10 significantly inhibited both IL-6 and TNF-alpha production in the THP-1 cell line stimulated by lipopolysaccharide and Ureaplasma urealyticum antigen. Similar effects were found in macrophages from tracheobronchial aspirate fluid from newborn infants. In the rat alveolar macrophage cell line, steroids inhibited IL-6 and TNF-alpha production, while rat rIL-10 did not significantly decrease production. In conclusion, steroids and human rIL-10 were able to downregulate proinflammatory cytokine production, which may explain the beneficial effect of steroids and suggests that rIL-10 could be tried as an anti-inflammatory agent in neonates with a high risk of CLD.
Li
Y H
YH
Neonatal Unit, Astrid Lindgren Children's Hospital, Karolinska Institutet, Stockholm, Sweden.
Brauner
A
A
Jonsson
B
B
Van der Ploeg
I
I
Söder
O
O
Holst
M
M
Jensen
J S
JS
Lagercrantz
H
H
Tullus
K
K
D000818:Animals; D000941:Antigens / Q000276:immunology; D019819:Budesonide / Q000494:pharmacology; D002460:Cell Line; D016207:Cytokines / Q000235:genetics*; D003907:Dexamethasone / Q000494:pharmacology; D005260:Female; D015870:Gene Expression / Q000187:drug effects*; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D016753:Interleukin-10 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000235:genetics; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000276:immunology / Q000378:metabolism*; D016676:Macrophages, Alveolar / Q000276:immunology / Q000378:metabolism; D008297:Male; D051381:Rats; D011994:Recombinant Proteins / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D016990:Ureaplasma urealyticum / Q000276:immunology
D000941:Antigens; D016207:Cytokines; D005938:Glucocorticoids; D015850:Interleukin-6; D008070:Lipopolysaccharides; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D019819:Budesonide; D003907:Dexamethasone