Prostaglandin modulation of airway inflammation and hyperresponsiveness in mice sensitized without adjuvant.

Abstract

As adjuvant during sensitization may cause unspecific immune reactions, the aim of the present study was to define the role of cyclooxygenase (COX) activity on airway inflammation and airway hyperresponsiveness (AHR) in an adjuvant-free allergic mouse model. Administration of diclofenac and indomethacin (non-selective COX inhibitors), FR122047 (COX-1 inhibitor) and lumiracoxib (selective COX-2 inhibitor) enhanced AHR. Only diclofenac and lumiracoxib reduced the inflammatory cell content of bronchoalveolar lavage (BAL). Moreover, levels of prostaglandins in BAL were reduced by indomethacin and FR122047 but were unaffected by lumiracoxib. However, compared with antigen controls, none of the COX inhibitors displayed major effects on the production of cytokines, smooth muscle mass, number of goblet cells and eosinophils, or collagen deposition in the airways. These data in mice sensitized without adjuvant support the fact that COX products have a general bronchoprotective role in allergic airway inflammation. Furthermore, the data suggest that COX-1 activity predominantly generates prostanoids in BAL, whereas COX-2 activity is associated with the accumulation of inflammatory cells in BAL. This study further supports that AHR on the one hand, and the inflammatory response and generation of prostanoids on the other, are dissociated and, at least in part, uncoupled events.

• Authors: Linda Swedin, Russ Ellis, Theresa Neimert-Andersson, Ake Ryrfeldt, Gunnar Nilsson, Mark Inman, Sven-Erik Dahlén, Mikael Adner
• Journal: Prostaglandins & other lipid mediators (Prostaglandins Other Lipid Mediat) Vol. 92 Issue 1-4 Pg. 44-53 (Jun 2010) ISSN: 1098-8823 [Print] United States
• PMID: 20214998 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2010 Elsevier Inc. All rights reserved.

Chemical References

• Adjuvants, Immunologic
• Cyclooxygenase Inhibitors
• Cytokines
• Leukotrienes
• Prostaglandins
• cysteinyl-leukotriene
• Methacholine Chloride
• Ovalbumin
• Cyclooxygenase 1
• Cyclooxygenase 2
• Cysteine

Topics

• Adjuvants, Immunologic
• Animals
• Bronchoalveolar Lavage
• Cyclooxygenase 1 (metabolism)
• Cyclooxygenase 2 (metabolism)
• Cyclooxygenase Inhibitors (administration & dosage, pharmacology, therapeutic use)
• Cysteine (metabolism)
• Cytokines (metabolism)
• Female
• Hypersensitivity (drug therapy, enzymology, immunology, metabolism)
• Immunization
• Inflammation (drug therapy, enzymology, immunology, metabolism)
• Leukotrienes (metabolism)
• Lung (drug effects, immunology, metabolism, pathology)
• Methacholine Chloride (immunology)
• Mice
• Mice, Inbred BALB C
• Ovalbumin (immunology)
• Prostaglandins (metabolism)
• Respiratory System (drug effects, enzymology, immunology, metabolism)