IL-4, IL-13, and dexamethasone augment fibroblast proliferation in asthma.
BACKGROUND
IL-4 and IL-13 have been shown to be critical for expression of the asthma phenotype in a murine model and may modulate human fibroblast function.


OBJECTIVE
We hypothesized that IL-4 and IL-13 would increase airway fibroblast proliferation and reduce the ability of dexamethasone to decrease this proliferation.


METHODS
Six subjects with severe asthma, 5 subjects with mild asthma, and 5 healthy subjects underwent bronchoscopy with endobronchial biopsy. Biopsy specimens were placed in Dulbecco modified Eagle medium and cultured, and only fibro-blasts from the first and second passages were evaluated. Cells were incubated with IL-4 (50 ng/mL), IL-13 (10 ng/mL), and the combination for 48 hours in the presence and absence of dexamethasone, 10(-7) mol/L, and 10(-8) mol/L. Fibroblasts were also incubated with IFN-gamma at 50 ng/mL to assess the response of a T(H)1 cytokine on proliferation.


RESULTS
Fibroblast proliferation, determined by (3)H-thymidine incorporation, was significantly increased by IL-4 in subjects with mild asthma as compared with IL-4 in subjects with severe asthma and healthy subjects (P =.003), IL-13 (P =.011), and the combination (P =.004). Dexamethasone also increased proliferation in the group with mild asthma as compared with the group with severe asthma and the healthy group (10(-7) mol/L, P =.02; 10(-8) mol/L, P =.02). IFN-gamma did not significantly alter airway fibroblast proliferation.


CONCLUSIONS
IL-4, IL-13, and dexamethasone all significantly increased fibroblast proliferation in subjects with mild asthma.
Kraft
M
M
Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado Health Sciences Center, 1400 Jackson St., Denver, CO 80206, USA.
Lewis
C
C
Pham
D
D
Chu
H W
HW
D000328:Adult; D001249:Asthma / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D003907:Dexamethasone / Q000494:pharmacology*; D005260:Female; D005347:Fibroblasts / Q000187:drug effects; D006801:Humans; D018793:Interleukin-13 / Q000494:pharmacology*; D015847:Interleukin-4 / Q000494:pharmacology*; D008297:Male
D018793:Interleukin-13; D015847:Interleukin-4; D003907:Dexamethasone