| Evaluation of inhaled carbon monoxide as an anti-inflammatory therapy in a nonhuman primate model of lung inflammation. | |
| | |
MedLine Citation:
|
PMID: 20729385 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Carbon monoxide (CO) confers anti-inflammatory protection in rodent models of lung injury when applied at low concentration. Translation of these findings to clinical therapies for pulmonary inflammation requires validation in higher mammals. We have evaluated the efficacy of inhaled CO in reducing LPS-induced lung inflammation in cynomolgus macaques. LPS inhalation resulted in profound neutrophil influx and moderate increases in airway lymphocytes, which returned to baseline levels within 2 wk following exposure. CO exposure (500 ppm, 6 h) following LPS inhalation decreased TNF-α release in bronchoalveolar lavage fluid but did not affect IL-6 or IL-8 release. Lower concentrations of CO (250 ppm, 6 h) did not reduce pulmonary neutrophilia. Pretreatment with budesonide, a currently used inhaled corticosteroid, decreased LPS-induced expression of TNF-α, IL-6, and IL-8, and reduced LPS-induced neutrophilia by ∼84%. In comparison, CO inhalation (500 ppm, for 6 h after LPS exposure) reduced neutrophilia by ∼67%. Thus, inhaled CO was nearly as efficacious as pretreatment with an inhaled corticosteroid at reducing airway neutrophil influx in cynomolgus macaques. However, the therapeutic efficacy of CO required relatively high doses (500 ppm) that resulted in high carboxyhemoglobin (COHb) levels (>30%). Lower CO concentrations (250 ppm), associated with anti-inflammatory protection in rodents, were ineffective in cynomolgus macaques and also yielded relatively high COHb levels. These studies highlight the complexity of interspecies variation of dose-response relationships of CO to COHb levels and to the anti-inflammatory functions of CO. The findings of this study warrant further investigations for assessing the therapeutic application of CO in nonhuman primate models of tissue injury and in human diseases. The study also suggests that akin to many new therapies in human diseases, the translation of CO therapy to human disease will require additional extensive and rigorous proof-of-concept studies in humans in the future. |
| | |
Authors:
|
Leah A Mitchell; Meghan M Channell; Christopher M Royer; Stefan W Ryter; Augustine M K Choi; Jacob D McDonald |
Related Documents
:
|
15829295 - Differential induction of apoptosis by lps and taxol in monocytic cells. 8799615 - Evidence for circulating hemocyte proliferation in the shrimp penaeus japonicus. 1569335 - Tolerance to endotoxin prevents mortality in infected thermal injury: association with ... 3327805 - Restoration of the lps responsive phenotype in c3h/hej macrophage hybrids: lps regulati... 12117905 - Up-regulation of fas (cd95) and induction of apoptosis in intestinal epithelial cells b... 18434235 - Airway epithelial cell inflammatory signalling in cystic fibrosis. |
Publication Detail:
|
Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-08-20 |
Journal Detail:
|
Title: American journal of physiology. Lung cellular and molecular physiology Volume: 299 ISSN: 1522-1504 ISO Abbreviation: Am. J. Physiol. Lung Cell Mol. Physiol. Publication Date: 2010 Dec |
Date Detail:
|
Created Date: 2010-12-06 Completed Date: 2011-01-13 Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 100901229 Medline TA: Am J Physiol Lung Cell Mol Physiol Country: United States |
Other Details:
|
Languages: eng Pagination: L891-7 Citation Subset: IM |
Affiliation:
|
Lovelace Respiratory Research Institute, Albuquerque, NM 87108, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Administration, Inhalation* Animals Bronchoalveolar Lavage Fluid / cytology Bronchodilator Agents / pharmacology, therapeutic use Budesonide / pharmacology, therapeutic use Carbon Monoxide* / administration & dosage, therapeutic use Disease Models, Animal* Humans Interleukin-6 / immunology Interleukin-8 / immunology Lipopolysaccharides / pharmacology Lung / drug effects, metabolism Macaca fascicularis Male Neutrophils / immunology Pneumonia* / drug therapy, immunology Tumor Necrosis Factor-alpha / immunology |
| Chemical | |
Reg. No./Substance:
|
0/Bronchodilator Agents; 0/Interleukin-6; 0/Interleukin-8; 0/Lipopolysaccharides; 0/Tumor Necrosis Factor-alpha; 51333-22-3/Budesonide; 630-08-0/Carbon Monoxide |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: The Ustilago maydis Clp1 protein orchestrates pheromone and b-dependent signaling pathways to coordi...
Next Document: Expression of IL-4/IL-13 receptors in differentiating human airway epithelial cells.