Human parainfluenza type 3 virus impairs the efficacy of glucocorticoids to limit allergy-induced pulmonary inflammation in guinea-pigs

Ford, William Richard ORCID: https://orcid.org/0000-0002-8792-6169, Blair, Alan Edward, Evans, Rhys L., John, Elinor, Bugert, Joachim Jakob ORCID: https://orcid.org/0000-0002-0556-3211, Broadley, Kenneth John ORCID: https://orcid.org/0000-0002-3339-2050 and Kidd, Emma Jane ORCID: https://orcid.org/0000-0001-5507-1170 2013. Human parainfluenza type 3 virus impairs the efficacy of glucocorticoids to limit allergy-induced pulmonary inflammation in guinea-pigs. Clinical Science 125 (10) , pp. 471-482. 10.1042/CS20130130

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Abstract

Viral exacerbations of allergen-induced pulmonary inflammation in pre-clinical models reportedly reduce the efficacy of glucocorticoids to limit pulmonary inflammation and airways hyper-responsiveness to inhaled spasmogens. However, exacerbations of airway obstruction induced by allergen challenge have not yet been studied. hPIV-3 (human parainfluenza type 3 virus) inoculation of guinea-pigs increased inflammatory cell counts in BAL (bronchoalveolar lavage) fluid and caused hyper-responsiveness to inhaled histamine. Both responses were abolished by treatment with either dexamethasone (20 mg/kg of body weight, subcutaneous, once a day) or fluticasone propionate (a 0.5 mg/ml solution aerosolized and inhaled over 15 min, twice a day). In ovalbumin-sensitized guinea-pigs, allergen (ovalbumin) challenge caused two phases of airway obstruction [measured as changes in sGaw (specific airways conductance) using whole body plethysmography]: an immediate phase lasting between 4 and 6 h and a late phase at about 7 h. The late phase, airway hyper-responsiveness to histamine and inflammatory cell counts in BAL were all significantly reduced by either glucocorticoid. Inoculation of guinea-pigs sensitized to ovalbumin with hPIV-3 transformed the allergen-induced airway obstruction from two transient phases into a single sustained response lasting up to 12 h. This exacerbated airway obstruction and airway hyper-responsiveness to histamine were unaffected by treatment with either glucocorticoid whereas inflammatory cell counts in BAL were only partially inhibited. Virus- or allergen-induced pulmonary inflammation, individually, are glucocorticoid-sensitive, but in combination generate a phenotype where glucocorticoid efficacy is impaired. This suggests that during respiratory virus infection, glucocorticoids might be less effective in limiting pulmonary inflammation associated with asthma.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Schools > Medicine Schools > Pharmacy
Subjects:	Q Science > QR Microbiology > QR180 Immunology R Medicine > RM Therapeutics. Pharmacology
Uncontrolled Keywords:	dexamethasone; fluticasone propionate; glucocorticoid resistance; parainfluenza type-3 virus; pulmonary inflammation
Publisher:	Biochemical Society
ISSN:	0143-5221
Last Modified:	11 Dec 2022 09:38
URI:	https://orca.cardiff.ac.uk/id/eprint/52135

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