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 (∼3.5 mL/kg), moderate (∼12.5 mL/kg), or high (∼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.
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Abbreviations
- VT:
-
tidal volume
- BPD:
-
bronchopulmonary dysplasia
- BALF:
-
bronchoalveolar lavage
- HFOV:
-
high frequency oscillatory ventilation
- LPS:
-
lipopolysaccharide
- NV:
-
non-ventilated
- MV:
-
mechanical ventilation
- LVT:
-
MV with low tidal volume
- MVT:
-
MV with moderate tidal volume
- HVT:
-
MV with high tidal volume
- LVT + LPS:
-
LVT after exposure to LPS
- LVT + O2:
-
LVT and 50% oxygen
- LVT + LPS/O2:
-
LVT and 50% oxygen after exposure to LPS
- PEEP:
-
positive end expiratory pressure
- MPO:
-
myeloperoxidase
- CXCL:
-
chemokine (C-X-C motif) ligand
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Supported by operating grants (MOP-15272) from the Canadian Institute of Health Research and the Sophia Children's Hospital Fund (SSWO) and infrastructure grants (CCURE, CSCCD) from the Canadian Foundation for Innovation. M.P. holds a Canadian Research Chair in Fetal, Neonatal and Maternal Health.
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Kroon, A., Wang, J., Huang, Z. et al. Inflammatory Response to Oxygen and Endotoxin in Newborn Rat Lung Ventilated With Low Tidal Volume. Pediatr Res 68, 63–69 (2010). https://doi.org/10.1203/PDR.0b013e3181e17caa
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DOI: https://doi.org/10.1203/PDR.0b013e3181e17caa
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