Comparative effects of inhaled budesonide and the NO-donating budesonide derivative, NCX 1020, against leukocyte influx and airway hyperreactivity following lipopolysaccharide challenge

Pulmonary Pharmacology & Therapeutics
B J Nevin, K J Broadley

Abstract

Lipopolysaccharide (LPS) inhalation (30 microg ml(-1), 1 h) caused airway hypereactivity (AHR) to histamine (1 mM, 20 s) 1 h later in conscious guinea-pigs. Bronchoalveolar lavage fluid (BALF) levels of neutrophils, myeloperoxidase (MPO) and protein were elevated whereas nitric oxide (NO) metabolites were reduced 1 h after LPS compared with saline challenge. 24 h after LPS, there was no AHR, but BALF neutrophils, eosinophils, macrophages, MPO, protein and NO metabolites were all raised. Budesonide (0.7 mM) and a molar equivalent concentration of the NO-donating budesonide derivative, NCX 1020, were inhaled (15 min) at 24 h and 45 min before LPS. The only change produced by budesonide was to reduce eosinophil influx at 24 h after LPS, compared with vehicle treated animals. NCX 1020, however, blocked AHR and reduced neutrophils (1 and 24 h) and MPO (1 and 24 h), while NO levels were raised at 1 and reduced at 24 h after LPS. The combined inhalation before LPS of the NO donor, SNAP (1.4 mM), with budesonide (0.7 mM) blocked the AHR to histamine and significantly reduced neutrophils (1 and 24 h) and MPO (1 and 24 h), while NO levels were raised at 1 h after LPS. Thus, NO and a corticosteroid co-administered as NCX 1020 or budesonid...Continue Reading

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Citations

Jun 27, 2009·European Journal of Clinical Pharmacology·Kian Fan ChungIan M Adcock
Jul 19, 2005·Expert Opinion on Investigational Drugs·Roberto ScatenaBruno Giardina
Jun 27, 2006·Pulmonary Pharmacology & Therapeutics·Néstor A Molfino, Peter K Jeffery
Mar 17, 2009·Respiratory Medicine·Louis-Philippe BouletPaolo M Renzi
Sep 23, 2008·Lancet·Ian M AdcockK Fan Chung
Dec 21, 2006·International Immunopharmacology·Nicola Smith, Kenneth J Broadley
May 23, 2012·Pharmacological Reviews·Mario CazzolaM Gabriella Matera
Sep 29, 2020·Journal of Experimental Pharmacology·Paola RoglianiLuigino Calzetta

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