Dissociation of airway inflammation and hyperresponsiveness by cyclooxygenase inhibition in allergen challenged mice

¹ The National Institute of Environmental Medicine, Division of Physiology, Karolinska Institutet, Stockholm, Sweden
² Dept of Medicine Solna, Clinical Immunology and Allergy Unit, Karolinska Institutet and University Hospital, Stockholm, Sweden
³ Dept of Medical Sciences, Clinical Physiology, Uppsala University, Uppsala, Sweden

^* To whom correspondence should be addressed. E-mail: linda.swedin{at}ki.se.

	Abstract

The aim of this study, in an eosinophil-driven allergic mouse model, 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. Inflammatory cells were assessed in bronchioalveolar lavage (BAL) and AHR was evaluated as the total lung resistance to methacholine (MCh)-challenge (Flexivent system).

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. Non-selective 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 study implicates distinct roles of prostanoids generated along the COX-1 and COX-2 pathways, and further that inflammatory cells in BAL do not change in parallel with AHR. The findings support that the AHR and the inflammatory response are distinct and at least in part uncoupled events.