IL-4, IL-13, and dexamethasone augment fibroblast proliferation in asthma

Abstract

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 fibroblasts 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, 10-7mol/L, and 10-8 mol/L. Fibroblasts were also incubated with IFN-γ at 50 ng/mL to assess the response of a TH1 cytokine on proliferation. Results: Fibroblast proliferation, determined by 3H-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-γ did not significantly alter airway fibroblast proliferation. Conclusion: IL-4, IL-13, and dexamethasone all significantly increased fibroblast proliferation in subjects with mild asthma.