Early phase resolution of mucosal eosinophilic inflammation in allergic rhinitis
Lena Uller*†1, Cecilia Ahlström Emanuelsson†2, Morgan Andersson2, Jonas S Erjefält1, Lennart Greiff2 and Carl G Persson3
Abstract Background: It is widely assumed that apoptosis ofeosinophils is a central component of resolution of allergic airway disease. However, this has not been demonstrated in human allergic airways in vivo. Based on animal in vivo observations we hypothesised that steroid-induced resolution of human airway eosinophilic inflammation involves inhibition of CCL5 (RANTES), a CC-chemokine regulating eosinophil and lymphocyte traffic, and elimination ofeosinophils without evident occurrence of apoptotic eosinophils in the diseased tissue. Objective: To determine mucosal eosinophilia, apoptotic eosinophils, general cell apoptosis and cell proliferation, and expression of CCL5 and CCL11 (eotaxin) in human allergic airway tissues in vivo at resolution of established symptomatic eosinophilic inflammation. Methods: Twenty-one patients with intermittent(birch and/or grass) allergic rhinitis received daily nasal allergen challenges for two seven days' periods separated by more than two weeks washout. Five days into these "artificial pollen seasons", nasal treatment with budesonide was instituted and continued for six days in a double blinded, randomized, placebo-controlled, and crossover design. This report is a parallel group comparison ofnasal biopsy histochemistry data obtained on the final day of the second treatment period. Results: Treatments were instituted when clinical rhinitis symptoms had been established. Compared to placebo, budesonide reduced tissue eosinophilia, and subepithelial more than epithelial eosinophilia. Steroid treatment also attenuated tissue expression of CCL5, but CCL11 was not reduced. General tissue cellapoptosis and epithelial cell proliferation were reduced by budesonide. However, apoptotic eosinophils were not detected in any biopsies, irrespective of treatment. Conclusions: Inhibition of CCL5-dependent recruitment of cells to diseased airway tissue, and reduced cell proliferation, reduced general cell apoptosis, but not increased eosinophil apoptosis, are involved in early phasesteroid-induced resolution of human allergic rhinitis. Background Airway tissue signs of established inflammation in asthma and allergic rhinitis include increased mucosal tissue cell turnover, eosinophilia, and increased chemokine production. Institution of steroid treatment eventually reduces both symptoms and eosinophilic inflammation in allergic airways diseases . However, early resolution effects invivo of this mainstay class of airway drugs are incompletely understood.
* Correspondence: email@example.com
Department of Experimental Medical Science, Lund University, Lund, Sweden Contributed equally
Full list of author information is available at the end of the article
In recent years, based largely on observations in vitro, the view that established airway tissue eosinophiliais resolved through steroid-induced apoptosis of these cells has been widely accepted [2-5]. Unexpectedly, therefore, we and others observed that steroid-treatment resolved established airway-pulmonary eosinophilic inflammation in murine in vivo models without inducing any detectable apoptosis of tissue eosinophils [6-8]. At neither spontaneous nor steroid-induced resolution were apoptoticeosinophils seen in the tissues in vivo [7,8]. Although these data were at variance with predictions made from in vitro experiments they were compatible with publicised human and animal in vivo-information in the field
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