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.
Treatment with intranasal iloprost reduces disease manifestations in a murine model of previously established COPD / M.R. Lammi, M.A. Ghonim, K. Pyakurel, A.S. Naura, S.V. Ibba, C.J. Davis, S.C. Okpechi, K.I. Happel, B.P. Deboisblanc, J. Shellito, A. Hamid Boulares. - In: AMERICAN JOURNAL OF PHYSIOLOGY. LUNG CELLULAR AND MOLECULAR PHYSIOLOGY. - ISSN 1040-0605. - 310:7(2016 Feb 05), pp. L630-L638.
|Titolo:||Treatment with intranasal iloprost reduces disease manifestations in a murine model of previously established COPD|
|Parole Chiave:||airway hyperresponsiveness; chronic obstructive pulmonary disorder; inflammation; prostacyclin; physiology; medicine (all); pulmonary and respiratory medicine; cell biology; physiology (medical)|
|Settore Scientifico Disciplinare:||Settore MED/04 - Patologia Generale|
|Data di pubblicazione:||5-feb-2016|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1152/ajplung.00297.2015|
|Appare nelle tipologie:||01 - Articolo su periodico|
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