Diminished transcription of interleukin-8 by monocytes from preterm neonates.
Developmental delays, which impair antibacterial host defense, are present in the neutrophil system of human preterm neonates. We hypothesized that diminished production of interleukin-8 (IL-8), a neutrophil chemotactic peptide, might in part be responsible for these defects. To test this, monocytes from the blood of preterm neonates, term neonates, and adults were isolated immunologically by "negative panning" and subsequently stimulated with interleukin-1 alpha (IL-1 alpha), tumor necrosis factor alpha (TNF-alpha), or lipopolysaccharide (LPS), after which IL-8 levels in the supernatants were measured by ELISA. Total cellular RNA was extracted and IL-8 mRNA was assessed by Northern blotting and by competitive polymerase chain reaction (PCR) analyses. After stimulation with IL-1 alpha, IL-8 accumulation was lowest in supernatants of monocytes from preterm neonates, intermediate in supernatants of monocytes from term neonates and greatest from monocytes of adults. Similarly, when stimulated with TNF-alpha or LPS, monocytes from preterm neonates produced less IL-8 than cells from term neonates and adults. These differences in IL-8 concentrations paralleled differences in IL-8 mRNA expression.
Schibler
K R
KR
Division of Human Development and Aging, University of Utah School of Medicine, Salt Lake City 84132.
Trautman
M S
MS
Liechty
K W
KW
White
W L
WL
Rothstein
G
G
Christensen
R D
RD
D000328:Adult; D001483:Base Sequence; D015152:Blotting, Northern; D004797:Enzyme-Linked Immunosorbent Assay; D004926:Escherichia coli; D005260:Female; D005312:Fetal Blood / Q000276:immunology*; D006801:Humans; D007231:Infant, Newborn / Q000097:blood / Q000276:immunology*; D007234:Infant, Premature / Q000097:blood / Q000276:immunology*; D007375:Interleukin-1 / Q000494:pharmacology; D016209:Interleukin-8 / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008969:Molecular Sequence Data; D009000:Monocytes / Q000187:drug effects / Q000276:immunology*; D009838:Oligodeoxyribonucleotides; D010920:Placenta; D016133:Polymerase Chain Reaction / Q000379:methods; D011247:Pregnancy; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D012016:Reference Values; D014158:Transcription, Genetic / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D007375:Interleukin-1; D016209:Interleukin-8; D008070:Lipopolysaccharides; D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha