Comparison of TNF antagonism by etanercept and dexamethasone on airway epithelium and remodeling in an experimental model of asthma.
BACKGROUND
The aim of the study was to compare the influence of TNF antagonism and corticosteroid treatment on epithelial, smooth muscle and basement membrane component of airway remodeling in an experimental murine model of chronic asthma.


METHODS
We used 30 BALB/c mice. Group 1 not exposed to ovalbumin or any medication was designated as control group. Chronic asthma model was achieved in the other three groups with intraperitoneal (IP) and inhaled ovalbumin. Then, Group 2 received IP saline, Group 3 received IP dexamethasone and Group 4 received IP etanercept. Epithelial, subepithelial smooth muscle and basement membrane thickness as well as goblet cells and mast cells were examined on samples isolated from left lung.


RESULTS
Etanercept treatment led to thinner epithelial and basement membrane layer and lower goblet and mast cell number than untreated asthmatic mice (p<0.001, p=0.001, p=0.005 and p=0.03 respectively). Neither epithelial and basement membrane thickness nor mast cell number was different among mice treated with etanercept and dexamethasone (p=0.38, p=0.79 and p=0.51 respectively). However, etanercept group was associated with thicker subepithelial muscle layer but lower goblet cell number (p<0.001 and p=0.04 respectively) than dexamethasone group.


CONCLUSIONS
Corticosteroids are more effective in decreasing smooth muscle mass while TNF antagonists in reducing goblet cell number in animal model of asthma. Therefore, further research is needed to assess the synergistic use of TNF antagonism and dexamethasone for more rational remodeling control.
MD, Celal Bayar University Medical Faculty, Dept. of Pediatric Allergy and Pulmonology, Manisa, Turkey.
Ozge
O
Yilmaz
Meral
M
Karaman
H Alper
HA
Bagriyanik
Fatih
F
Firinci
Muge
M
Kiray
Ahmet
A
Turkeli
Ozkan
O
Karaman
Hasan
H
Yuksel
D056151:Airway Remodeling / Q000187:drug effects*; D000485:Allergens / Q000276:immunology; D000818:Animals; D001249:Asthma / Q000473:pathology*; D002452:Cell Count; D003907:Dexamethasone / Q000494:pharmacology*; D004195:Disease Models, Animal; D000068800:Etanercept; D005938:Glucocorticoids / Q000494:pharmacology*; D020397:Goblet Cells / Q000187:drug effects / Q000473:pathology; D007074:Immunoglobulin G / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects / Q000473:pathology; D008407:Mast Cells / Q000187:drug effects / Q000473:pathology; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology; D018124:Receptors, Tumor Necrosis Factor; D020545:Respiratory Mucosa / Q000187:drug effects / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
D000485:Allergens; D005938:Glucocorticoids; D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D003907:Dexamethasone; D010047:Ovalbumin; D000068800:Etanercept
Inflammation; Mouse model of asthma; Remodeling; Steroid; Tumor necrosis factor