Developmental differences in the responses of IL-6 and IL-13 transgenic mice exposed to hyperoxia.
Our previous work has shown that adult mice with overexpression of IL-6 and IL-13 in the lung have enhanced survival in hyperoxia associated with reduced hyperoxia-induced lung injury and cell death. We hypothesized that there are developmental differences in these responses in the adult vs. the newborn (NB) animal, and these responses have clinical relevance in the human NB. We compared the responses to 100% O(2) of NB IL-6 and IL-13 transgenic mice with wild-type littermate controls by evaluating mortality, lung tissue TUNEL staining, and mRNA expression using RT-PCR. We used ELISA to measure IL-6 levels in tracheal aspirates from human neonates. Our results show that, in contrast to the cytoprotective effects in mature mice, IL-6 caused significantly increased mortality, DNA injury, caspases, cell death regulator and angiogenic factor expression in hyperoxia in the NB. Furthermore, tracheal aspirate levels of IL-6 were significantly increased in premature neonates with respiratory distress syndrome who had an adverse outcome (bronchopulmonary dysplasia/death). In contrast to the protective effects in adults, there was no survival advantage to the NB IL-13 mice in hyperoxia. These findings imply that caution should be exercised in extrapolating results from the adult to the NB.
Choo-Wing
Rayman
R
Department of Pediatrics, Division of Perinatal Medicine, Yale University School of Medicine, New Haven, Connecticut 06520-8064, USA.
Nedrelow
Jonathan H
JH
Homer
Robert J
RJ
Elias
Jack A
JA
Bhandari
Vineet
V
D043925:Angiogenesis Inducing Agents / Q000378:metabolism; D042702:Angiopoietin-2 / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D018496:Hyperoxia / Q000378:metabolism* / Q000473:pathology*; D007231:Infant, Newborn; D018793:Interleukin-13 / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism*; D008168:Lung / Q000254:growth & development* / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D012127:Respiratory Distress Syndrome, Newborn / Q000201:enzymology; D016019:Survival Analysis
D043925:Angiogenesis Inducing Agents; D042702:Angiopoietin-2; D051017:Apoptosis Regulatory Proteins; D018793:Interleukin-13; D015850:Interleukin-6; D004247:DNA; D053148:Caspase 3