Early phase resolution of mucosal eosinophilic inflammation in allergic rhinitis.
BACKGROUND
It is widely assumed that apoptosis of eosinophils 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 of eosinophils 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 of nasal 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 cell apoptosis 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 phase steroid-induced resolution of human allergic rhinitis.
Uller
Lena
L
Department of Experimental Medical Science, Lund University, Lund, Sweden. lena.uller@med.lu.se
Emanuelsson
Cecilia Ahlström
CA
Andersson
Morgan
M
Erjefält
Jonas S
JS
Greiff
Lennart
L
Persson
Carl G
CG
D000281:Administration, Intranasal; D000328:Adult; D018926:Anti-Allergic Agents / Q000008:administration & dosage*; D052179:Antigens, Plant / Q000276:immunology*; D017209:Apoptosis / Q000187:drug effects; D029662:Betula / Q000276:immunology*; D001706:Biopsy; D019819:Budesonide / Q000008:administration & dosage*; D049109:Cell Proliferation / Q000187:drug effects; D054413:Chemokine CCL11 / Q000378:metabolism; D018946:Chemokine CCL5 / Q000378:metabolism; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004802:Eosinophilia / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D007249:Inflammation / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D008297:Male; D017817:Nasal Lavage Fluid / Q000166:cytology / Q000276:immunology; D009297:Nasal Mucosa / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D015990:Placebo Effect; D006109:Poaceae / Q000276:immunology*; D011058:Pollen / Q000276:immunology*; D006255:Rhinitis, Allergic, Seasonal / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
D018926:Anti-Allergic Agents; D052179:Antigens, Plant; C515456:CCL11 protein, human; C483024:CCL5 protein, human; D054413:Chemokine CCL11; D018946:Chemokine CCL5; D019819:Budesonide
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