Inflammatory response to oxygen and endotoxin in newborn rat lung ventilated with low tidal volume.

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.