Dissociation of airway inflammation and hyperresponsiveness by cyxloogynease 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.

Neimert Andersson, TheresaKarolinska Institutet (författare)
Hjoberg, JosephineUppsala universitet,Klinisk fysiologi(Swepub:uu)josehjob (författare)
Jonasson, SofiaUppsala universitet,Klinisk fysiologi(Swepub:uu)sojon516 (författare)
Van Hage, MarianneKarolinska Institutet (författare)
Adner, MikaelKarolinska Institutet (författare)
Ryrfeldt, ÅkeKarolinska Institutet (författare)
Dahlén, Sven-ErikKarolinska Institutet (författare)
Karolinska InstitutetKlinisk fysiologi (creator_code:org_t)

Ingår i:European Respiratory Journal: European Respiratory Society (ERS)34:1, s. 200-2080903-19361399-3003

Av författaren/redakt...: Swedin, Linda; Neimert Andersso ...; Hjoberg, Josephi ...; Jonasson, Sofia; Van Hage, Marian ...; Adner, Mikael; visa fler...; Ryrfeldt, Åke; Dahlén, Sven-Eri ...; visa färre...

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