title: 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: Louisiana State University Health Sciences Center, New Orleans, Lousiana; mlammi@lsuhsc.edu.
authors: Matthew R
authors: MR
authors: Lammi
authors: Louisiana State University Health Sciences Center, New Orleans, Lousiana; Stanley Scott Cancer Center, New Orleans, Louisiana; and.
authors: Mohamed A
authors: MA
authors: Ghonim
authors: Louisiana State University Health Sciences Center, New Orleans, Lousiana; Stanley Scott Cancer Center, New Orleans, Louisiana; and.
authors: Kusma
authors: K
authors: Pyakurel
authors: Panjab University, Chandigarh, India.
authors: Amarjit S
authors: AS
authors: Naura
authors: Louisiana State University Health Sciences Center, New Orleans, Lousiana; Stanley Scott Cancer Center, New Orleans, Louisiana; and.
authors: Salome V
authors: SV
authors: Ibba
authors: Louisiana State University Health Sciences Center, New Orleans, Lousiana; Stanley Scott Cancer Center, New Orleans, Louisiana; and.
authors: Christian J
authors: CJ
authors: Davis
authors: Louisiana State University Health Sciences Center, New Orleans, Lousiana; Stanley Scott Cancer Center, New Orleans, Louisiana; and.
authors: Samuel C
authors: SC
authors: Okpechi
authors: Louisiana State University Health Sciences Center, New Orleans, Lousiana;
authors: Kyle I
authors: KI
authors: Happel
authors: Louisiana State University Health Sciences Center, New Orleans, Lousiana;
authors: Bennett P
authors: BP
authors: deBoisblanc
authors: Louisiana State University Health Sciences Center, New Orleans, Lousiana;
authors: Judd
authors: J
authors: Shellito
authors: Louisiana State University Health Sciences Center, New Orleans, Lousiana; Stanley Scott Cancer Center, New Orleans, Louisiana; and.
authors: A Hamid
authors: AH
authors: Boulares
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D016285:Iloprost / Q000008:administration & dosage*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D008810:Mice, Inbred C57BL; D020556:Neutrophil Infiltration; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000276:immunology; D012130:Respiratory Hypersensitivity / Q000188:drug therapy / Q000276:immunology
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D008070:Lipopolysaccharides; D016285:Iloprost
keywords: airway hyperresponsiveness; chronic obstructive pulmonary disorder; inflammation; prostacyclin