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Airway function and reactivity, leukocyte influx and nitric oxide after inoculation with parainfluenza-3 virus: effects of dexamethasone or rolipram

Toward, Toby J., Johnson, Frederick J., Boult, J. E. and Maillard, Jean-Yves 2005. Airway function and reactivity, leukocyte influx and nitric oxide after inoculation with parainfluenza-3 virus: effects of dexamethasone or rolipram. International Immunopharmacology 5 (4) , pp. 771-782. 10.1016/j.intimp.2004.12.006

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Abstract

Guinea-pigs were inoculated with parainfluenza type 3 (PI3) virus (5.2 x 10(7)) or medium (125 microl each nostril). The PDE4-inhibitor, rolipram (1 mg kg(-1)), the corticosteroid, dexamethasone (20 mg kg(-1)), or vehicle were administered (i.p.) 24 h and 0.5 h before inoculation and for 4 days thereafter. Respiratory function, recorded in conscious guinea-pigs as specific airways conductance (sGaw) by whole-body plethysmography, was unaffected over 4 days by inoculation with medium or PI3. Inhaled histamine (nose-only, 1 mM, 20 s) 24 h before inoculation produced no response but 4 days after PI3 inoculation, a significant (P<0.001) bronchoconstriction occurred, indicating airway hyperreactivity (AHR). Dexamethasone or rolipram treatment inhibited the AHR. Four days after PI3- or medium-inoculation, animals underwent bronchoalveolar lavage (BAL) for total and differential (macrophages, eosinophils and neutrophils) cell counts and determination of nitric oxide (NO) as nitrite and nitrate. Compared with medium-inoculated animals, BAL fluid removed 4 days after PI3 inoculation had significantly increased macrophages, eosinophils and neutrophils. Dexamethasone or rolipram significantly (P<0.05) reduced the PI3-induced airways influx of macrophages (by 40% and 47%), eosinophils (79% and 84%) and neutrophils (58% and 61%). PI3-inoculation significantly (P<0.05) increased BALF combined NO metabolites (84.8+/-2.2 microM 100 microl(-1)), compared with medium-inoculated (56.0+/-5.8) or naive animals (45.7+/-2.0). Treating the PI3-infected guinea-pigs with dexamethasone or rolipram significantly (P<0.001) reduced the raised NO metabolites by 34% and 37%, respectively. These results support a role for steroids and PDE4-inhibitors in the management of inflammation and airways hyperreactivity arising from viral infection of the airways.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Pharmacy
Subjects: R Medicine > RS Pharmacy and materia medica
Uncontrolled Keywords: Parainfluenza virus; Guinea-pig airways; Rolipram; Dexamethasone; Nitric oxide; Airway hyperreactivity; Leukocyte infiltration
Publisher: Elsevier
ISSN: 1567-5769
Last Modified: 04 Jun 2017 03:01
URI: http://orca.cf.ac.uk/id/eprint/15441

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