Treatment with intranasal iloprost reduces disease manifestations in a murine model of previously established COPD.

Abstract

Pulmonary endothelial prostacyclin appears to be involved in the pathogenesis of chronic obstructive pulmonary disease (COPD). The effect of treatment with a prostacyclin analog in animal models of previously established COPD is unknown. We evaluated the short- and long-term effect of iloprost on inflammation and airway hyperresponsiveness (AHR) in a murine model of COPD. Nineteen mice were exposed to LPS/elastase, followed by either three doses of intranasal iloprost or saline. In the long-term treatment experiment, 18 mice were exposed to LPS/elastase and then received 6 wk of iloprost or were left untreated as controls. In the short-term experiment, iloprost did not change AHR but significantly reduced serum IL-5 and IFN-γ. Long-term treatment with iloprost for both 2 and 6 wk significantly improved AHR. After 6 wk of iloprost, there was a reduction in bronchoalveolar lavage (BALF) neutrophils, serum IL-1β (30.0 ± 9.2 vs. 64.8 ± 7.4 pg/ml, P = 0.045), IL-2 (36.5 ± 10.6 vs. 83.8 ± 0.4 pg/ml, P = 0.01), IL-10 (75.7 ± 9.3 vs. 96.5 ± 3.5 pg/ml, P = 0.02), and nitrite (15.1 ± 5.4 vs. 30.5 ± 10.7 μmol, P = 0.01). Smooth muscle actin (SMA) in the lung homogenate was also significantly reduced after iloprost treatment (P = 0.02), and SMA thickness was reduced in the small and medium blood vessels after iloprost (P < 0.001). In summary, short- and long-term treatment with intranasal iloprost significantly reduced systemic inflammation in an LPS/elastase COPD model. Long-term iloprost treatment also reduced AHR, serum nitrite, SMA, and BALF neutrophilia. These data encourage future investigations of prostanoid therapy as a novel treatment for COPD patients.

• Authors: Matthew R Lammi, Mohamed A Ghonim, Kusma Pyakurel, Amarjit S Naura, Salome V Ibba, Christian J Davis, Samuel C Okpechi, Kyle I Happel, Bennett P deBoisblanc, Judd Shellito, A Hamid Boulares
• Journal: American journal of physiology. Lung cellular and molecular physiology (Am J Physiol Lung Cell Mol Physiol) Vol. 310 Issue 7 Pg. L630-8 (04 01 2016) ISSN: 1522-1504 [Electronic] United States
• PMID: 26851260 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2016 the American Physiological Society.

Chemical References

• Anti-Inflammatory Agents
• Cytokines
• Lipopolysaccharides
• Iloprost

Topics

• Administration, Intranasal
• Animals
• Anti-Inflammatory Agents (administration & dosage)
• Cytokines (metabolism)
• Disease Models, Animal
• Drug Evaluation, Preclinical
• Iloprost (administration & dosage)
• Lipopolysaccharides (pharmacology)
• Male
• Mice, Inbred C57BL
• Neutrophil Infiltration
• Pulmonary Disease, Chronic Obstructive (drug therapy, immunology)
• Respiratory Hypersensitivity (drug therapy, immunology)