title: Inflammatory response to oxygen and endotoxin in newborn rat lung ventilated with low tidal volume.
abstract: Herein, we determined the contribution of mechanical ventilation, hyperoxia and inflammation, individually or combined, to the cytokine/chemokine response of the neonatal lung. Eight-day-old rats were ventilated for 8 h with low ( approximately 3.5 mL/kg), moderate ( approximately 12.5 mL/kg), or high ( approximately 25 mL/kg) tidal volumes (VT) and the cytokine/chemokine response was measured. Next, we tested whether low-VT ventilation with 50% oxygen or a preexisting inflammation induced by lipopolysaccharide (LPS) would modify this response. High-, moderate-, and low-VT ventilation significantly elevated CXCL-2 and IL-6 mRNA levels. Low-VT ventilation with 50% oxygen significantly increased IL-6 and CXCL-2 expression versus low-VT ventilation alone. LPS pretreatment combined with low-VT ventilation with 50% oxygen amplified IL-6 mRNA expression when compared with low VT alone or low VT + 50% O2 treatment. In contrast, low VT up-regulated CXCL-2 levels were reduced to nonventilated levels when LPS-treated newborn rats were ventilated with 50% oxygen. Thus, low-VT ventilation triggers the expression of acute phase cytokines and CXC chemokines in newborn rat lung, which is amplified by oxygen but not by a preexisting inflammation. Depending on the individual cytokine or chemokine, the combination of both oxygen and inflammation intensifies or abrogates the low VT-induced inflammatory response.
authors.affiliation: Lung Biology Research, Physiology and Experimental Medicine Program, Hospital for Sick Children Research Institute, Toronto, Ontario M5G 1X8, Canada.
authors.forename: Andreas A
authors.initials: AA
authors.lastname: Kroon
authors.forename: Jinxia
authors.initials: J
authors.lastname: Wang
authors.forename: Zhen
authors.initials: Z
authors.lastname: Huang
authors.forename: Lei
authors.initials: L
authors.lastname: Cao
authors.forename: Maciej
authors.initials: M
authors.lastname: Kuliszewski
authors.forename: Martin
authors.initials: M
authors.lastname: Post
mesh_terms: D000818:Animals; D000831:Animals, Newborn / Q000276:immunology*; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D001997:Bronchopulmonary Dysplasia / Q000276:immunology / Q000503:physiopathology; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007231:Infant, Newborn; D007249:Inflammation / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000276:immunology / Q000494:pharmacology; D008168:Lung / Q000166:cytology / Q000187:drug effects* / Q000276:immunology*; D010100:Oxygen / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012121:Respiration, Artificial; D013990:Tidal Volume / Q000502:physiology*
chemical_list: D016207:Cytokines; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D010100:Oxygen