Ventilation-induced Alterations in Lung Development

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 hours with low (~3.5 ml.kg-1), moderate (~12.5 ml.kg-1) or high (~25 ml.kg-1) tidal volumes (VT) and the cytokine/ chemokine response was measured. Next, we tested whether low VT ventilation with 50% oxygen or a pre-existing 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 vs. low VT ventilation alone. LPS pre-treatment combined with low VT ventilation with 50% oxygen amplified IL-6 mRNA expression when compared to low VT alone or low VT+50% O2 treatment. In contrast, low VTupregulated CXCL-2 levels were reduced to non-ventilated 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 pre-existing inflammation. Depending on the individual cytokine or chemokine, the combination of both oxygen and inflammation intensifies or abrogates the low VT-induced inflammatory response. Inflammatory Response to Oxygen and Endotoxin in Newborn rat Lung ventilated with Low Tidal Volume 41