Interleukin-4 and -13 expression is co-localized to mast cells within the airway smooth muscle in asthma.
BACKGROUND
Airway smooth muscle infiltration by mast cells is a feature of asthma and not eosinophilic bronchitis. In asthma, Th2 cytokines have been implicated as playing a critical role in the development of airway inflammation and hyper-responsiveness. Whether inflammatory cells within the airway smooth muscle release these cytokines is unknown.


METHODS
We have undertaken a comparative immunohistochemical study in bronchial biopsies from 14 subjects with asthma, 10 with eosinophilic bronchitis and eight normal controls recruited from two centres.


RESULTS
The median number of IL-4+ cells/mm2 smooth muscle was significantly higher in subjects with asthma than eosinophilic bronchitis and normal controls for both the anti-IL-4 mAb 3H4 (2.4, 0, 0, respectively; P=0.001) and anti-IL-4 mAb 4D9 (1.6, 0, 0, respectively; P=0.02). There were no group differences in the number of IL-5+ cells (P=0.31). In six subjects with asthma, IL-13 expression by cells within the airway smooth muscle was studied. The median (range) of IL-13+cells was 2 (0.9-2.7). Ninety-four percent of the cells expressing IL-4 (3H4), 92% of those expressing IL-4 (4D9) and 100% expressing IL-13 in the airway smooth muscle were mast cells. Fifty-five percent of the mast cells within the airway smooth muscle co-localized to IL-4 (3H4), 29% to IL-4 (4D9) and 17% to IL-13.


CONCLUSIONS
In asthma, IL-4+ and IL-13+ cells were present within the airway smooth muscle and were expressed predominantly by mast cells, suggesting that IL-4 and IL-13 may play an important role in mast cell-airway smooth muscle interactions.
Brightling
C E
CE
Institute for Lung Health, Leicester-Warwick Medical School and University Hospitals of Leicester, Leicester, UK. cab17@le.ac.uk
Symon
F A
FA
Holgate
S T
ST
Wardlaw
A J
AJ
Pavord
I D
ID
Bradding
P
P
D000328:Adult; D001249:Asthma / Q000276:immunology*; D001980:Bronchi / Q000276:immunology*; D001991:Bronchitis / Q000276:immunology; D016022:Case-Control Studies; D004804:Eosinophils / Q000276:immunology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D018793:Interleukin-13 / Q000032:analysis*; D015847:Interleukin-4 / Q000032:analysis*; D015848:Interleukin-5 / Q000276:immunology; D008297:Male; D008407:Mast Cells / Q000276:immunology*; D008875:Middle Aged; D009130:Muscle, Smooth / Q000276:immunology*; D018709:Statistics, Nonparametric; D018418:Th2 Cells / Q000276:immunology
D018793:Interleukin-13; D015848:Interleukin-5; D015847:Interleukin-4