Correlation of augmented IL-8 production to premature chronic lung disease: implication of posttranscriptional regulation.
Despite that advances in neonatal medicine have significantly reduced the early mortality of premature infants, a considerable number of them are still prone to develop chronic lung disease (CLD) later. To find a method of early prevention, we investigated the efficacy of using certain early proinflammatory responses to predict the development of CLD. In the present study, 34 premature infants who required endotracheal intubation within 4 h of birth were recruited for analysis of IL-8, IL-10, and TNF-alpha levels in their bronchoalveolar lavage (BAL) fluid and blood. It was found that level of IL-8 but not TNF-alpha or IL-10 in initial BAL fluid was significantly correlated to neutrophils in the BAL and inversely correlated to the gestational age of prematurity. Elevation of IL-8 level in BAL on the first day of life was correlated to the development of CLD. Further studies showed that neonatal cord blood released significantly higher IL-8 but lower TNF-alpha levels after stimulation by endotoxin. The augmented IL-8 mRNA expression in cord blood was inhibited by actinomycin D but enhanced by cycloheximide, suggesting that IL-8 production is controlled by de novo transcriptional induction as well as posttranscriptional up-regulation of IL-8 by neonatal leukocytes, relating to the development of CLD. Thus, an appropriate modulation of initial IL-8 production in premature infants might be beneficial for the prevention of the development of CLD.
Huang
Hsin-Chun
HC
Department of Pediatrics, Chang-Gung Memorial Hospital and Graduate Institute of Clinical Medical Science, Chang Gung University at Kaohsiung, Kaohsiung 833, Taiwan.
Tai
Fang-Yu
FY
Wang
Feng-Sheng
FS
Liu
Chieh-An
CA
Hsu
Te-Yao
TY
Ou
Chia-Yo
CY
Yang
Kuender D
KD
D000328:Adult; D001992:Bronchoalveolar Lavage Fluid; D002908:Chronic Disease; D003513:Cycloheximide / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism; D003609:Dactinomycin / Q000494:pharmacology; D004731:Endotoxins / Q000378:metabolism; D005260:Female; D005312:Fetal Blood / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation; D005865:Gestational Age; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D016753:Interleukin-10 / Q000096:biosynthesis; D016209:Interleukin-8 / Q000096:biosynthesis* / Q000378:metabolism; D007962:Leukocytes / Q000378:metabolism; D008171:Lung Diseases / Q000378:metabolism*; D008297:Male; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012323:RNA Processing, Post-Transcriptional; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014158:Transcription, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000378:metabolism; D015854:Up-Regulation
D016207:Cytokines; D004731:Endotoxins; D016209:Interleukin-8; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D003609:Dactinomycin; D003513:Cycloheximide