Anti-inflammatory effects of inhaled nitric oxide are optimized at lower oxygen concentration in experimental Klebsiella pneumoniae pneumonia.
OBJECTIVE
To evaluate whether antiinflammatory effects of inhaled nitric oxide (NO) in experimental Klebsiella pneumoniae pneumonia may be affected by oxygen levels in association with cytokine response and NO synthase (NOS) activity.


METHODS
Healthy adult rats were intratracheally instilled with live Klebsiella pneumoniae to induce pneumonia (P) or with sterile saline as a control (C) group. Group C was allocated to room air (CA) and inhaled NO (CNO, NO = 20 parts per million) groups. Group P was divided into 6 groups (n = 8 - 10) exposed to room air (PA), inhaled NO (PNO), low oxygen (40%, PLO), inhaled NO and low oxygen (PLONO), high oxygen (100%, PHO), and inhaled NO and high oxygen (98%, PHONO). After 24 h exposure, intraalveolar cells, expression of proinflammatory cytokines, nuclear transcription factor (NF-kappaB), myeloperoxidase (MPO) and NOS activities, characteristic of lung inflammatory mechanisms, were measured.


RESULTS
All the pneumonia groups had pneumonia whereas CA and CNO had no or mild lung inflammation. Compared to the PA, significantly decreased recruitment of alveolar neutrophils was found in the PNO, along with lower NF-kappaB and MPO activity, tumor necrosis factor-alpha (TNF-alpha) and intercellular adhesion molecule-1 (ICAM-1). Similar trends were found between the PLONO and PLO in alleviation of lung inflammation. However, PHONO significantly enhanced recruitment of alveolar neutrophils and pulmonary MPO activity associated with increased TNF-alpha. Inhaled NO improved bacterial clearance, reduced total proteins in alveoli, and ICAM-1 expression irrespective of oxygen levels. Inhaled NO and/or low and high oxygen partially restored constitutive NOS activity whereas high oxygen or together with inhaled NO depressed inducible NOS activity.


CONCLUSIONS
The overall beneficial effects of inhaled NO in anti-inflammation in the mature lungs with K. pneumoniae pneumonia are in favor of a combination with lower level of oxygen, which warrants clinical verification in the treatment of lung inflammatory injury.
Sun
Z
Z
Laboratory of Pediatric Respiratory and Intensive Care Medicine, Children's Hospital of Fudan University, Shanghai, 200032, China.
Sun
B
B
Wang
X
X
Wang
W
W
Zhu
L
L
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007710:Klebsiella Infections / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D007711:Klebsiella pneumoniae; D007958:Leukocyte Count; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D010100:Oxygen / Q000494:pharmacology; D009195:Peroxidase / Q000378:metabolism; D010713:Phosphatidylcholines / Q000032:analysis; D010743:Phospholipids / Q000032:analysis; D018410:Pneumonia, Bacterial / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D011506:Proteins / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016328:NF-kappa B; D010713:Phosphatidylcholines; D010743:Phospholipids; D011506:Proteins; D014409:Tumor Necrosis Factor-alpha; C017463:lecithins, disaturated; D018799:Intercellular Adhesion Molecule-1; D009569:Nitric Oxide; D009195:Peroxidase; D019001:Nitric Oxide Synthase; D010100:Oxygen