Dissociation of airway inflammation and hyperresponsiveness by cyclooxygenase inhibition in allergen challenged mice.
The aim of the current study was to define how cyclooxygenase (COX)-activity affects airway hyperresponsiveness (AHR) and inflammation using interventions with COX inhibitors at different time points during allergen challenge and/or prior to measurement of AHR in an eosinophil-driven allergic mouse model. Inflammatory cells were assessed in bronchioalveolar lavage (BAL) and AHR was evaluated as the total lung resistance to methacholine (MCh) challenge. Administration of FR122047 (COX-1 inhibitor) during ovalbumin (OVA) challenge and prior to MCh challenge enhanced AHR without affecting the inflammatory cell response. In contrast, administration of lumiracoxib (COX-2 inhibitor) during the same time period had no effect on AHR but reduced the inflammatory cells in BAL. Nonselective COX inhibition with diclofenac both enhanced the AHR and reduced the inflammatory cells. Administration of diclofenac only during OVA challenge reduced the cells in BAL without any changes in AHR, whereas administration of diclofenac only prior to MCh challenge enhanced AHR but did not affect the cells in BAL. The present study implicates distinct roles of prostanoids generated along the COX-1 and COX-2 pathways and, furthermore, that inflammatory cells in BAL do not change in parallel with AHR. These findings support the fact that AHR and the inflammatory response are distinct and, at least in part, uncoupled events.
Swedin
L
L
The National Institute of Environmental Medicine, Division of Physiology, Scheeles väg 1, Box 287, Karolinska Institutet, SE-171 77 Stockholm, Sweden. linda.swedin@ki.se
Neimert-Andersson
T
T
Hjoberg
J
J
Jonasson
S
S
van Hage
M
M
Adner
M
M
Ryrfeldt
A
A
Dahlén
S-E
SE
D000485:Allergens / Q000737:chemistry; D000818:Animals; D016535:Bronchial Hyperreactivity / Q000276:immunology* / Q000473:pathology; D018893:Bronchoalveolar Lavage; D051545:Cyclooxygenase 1 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D004008:Diclofenac / Q000494:pharmacology; D005260:Female; D007073:Immunoglobulin E / Q000378:metabolism; D007074:Immunoglobulin G / Q000378:metabolism; D007249:Inflammation / Q000276:immunology* / Q000473:pathology; D016210:Methacholine Chloride / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C
D000485:Allergens; D016861:Cyclooxygenase Inhibitors; D007074:Immunoglobulin G; D016210:Methacholine Chloride; D004008:Diclofenac; D007073:Immunoglobulin E; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2