Development and characterisation of a novel and rapid lung eosinophil influx model in the rat.
Eosinophils play a major role in the development and severity of asthma. Robust and rapid preclinical animal models are desirable to profile novel therapeutics inhibiting the influx of eosinophils into the airways. To develop a rapid, airway eosinophil recruitment model in the rat, Brown-Norway (BN) rats were immunised with ovalbumin (OVA)/alum on day 0, 1 and 2 and challenged with OVA aerosol on day 5 and 6. On day 7 bronchoalveolar lavage fluid (BALF) was analysed for eosinophil numbers, eosinophil peroxidase (EPO) activity and cytokines. Lung sections were also examined. The immunised animals showed a strong selective influx of eosinophils into the airways correlating with enhanced EPO activity, Interleukin (IL-4), IL-5 and monocytes chemo attractant protein levels in the BALF in comparison to sham-sensitised rats. In addition the immunised rats developed goblet cell metaplasia in the lung and showed OVA specific IgG1 and IgE levels in the serum but no airway hyperreactivity after metacholine challenge. Airway inflammation was suppressed by applying the steroids Budesonide (intra tracheally) and Prednisolone (per orally), Roflumilast a phosphodiesterase-4 inhibitor, and the H1 receptor antagonists Epinastine and Ketotifen. Montelukast, a Leukotriene receptor antagonist and Chromoglycate, a mast cell stabiliser, had no effect in this model. In summary, in this novel preclinical rat model therapeutics expected to inhibit the development of airway eosinophilia can rapidly be tested.
Werner-Klein
Melanie
M
Department of Pulmonary Research, Boehringer Ingelheim Pharma GmbH & Co. KG, H91-02-01, Birkendorferstr. 65, D-88397 Biberach a.d. Riss, Germany.
Göggel
Rolf
R
Westhof
Andreas
A
Erb
Klaus J
KJ
D000534:Alum Compounds; D000631:Aminopyridines / Q000494:pharmacology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001249:Asthma / Q000188:drug therapy / Q000503:physiopathology*; D001549:Benzamides / Q000494:pharmacology; D001992:Bronchoalveolar Lavage Fluid; D019819:Budesonide / Q000494:pharmacology; D003521:Cyclopropanes / Q000494:pharmacology; D003984:Dibenzazepines / Q000494:pharmacology; D004195:Disease Models, Animal; D004804:Eosinophils / Q000378:metabolism*; D006634:Histamine H1 Antagonists; D007093:Imidazoles / Q000494:pharmacology; D007665:Ketotifen / Q000494:pharmacology; D008168:Lung / Q000187:drug effects / Q000503:physiopathology; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011239:Prednisolone / Q000494:pharmacology; D051381:Rats; D011914:Rats, Inbred BN
D000534:Alum Compounds; D000631:Aminopyridines; D000893:Anti-Inflammatory Agents; D001549:Benzamides; D003521:Cyclopropanes; D003984:Dibenzazepines; D006634:Histamine H1 Antagonists; D007093:Imidazoles; D010726:Phosphodiesterase Inhibitors; C424423:Roflumilast; C041524:aluminum sulfate; D019819:Budesonide; D010047:Ovalbumin; D011239:Prednisolone; C053090:epinastine; D007665:Ketotifen