Expression of interleukin-4 in scleroderma skin specimens and scleroderma fibroblast cultures - Potential role in fibrosis

Background: Scleroderma (systemic sclerosis) is a fibrotic disease characterized by an uncontrolled tissular accumulation of collagen. Several cytokines have been implicated in the fibroblast activation leading to fibrosis. For instance, we have previously demonstrated that interleukin-4 (IL-4) is a potent activator of collagen synthesis in fibroblast cultures. In this study, using immunocytochemical methods and in situ hybridization, we investigated the expression of IL-4 in normal and scleroderma skin and fibroblast cultures. Observations: Immunocytochemical studies with anti-IL-4 antibody were performed on biopsy specimens from 9 patients with normal skin and 11 patients with scleroderma. The label was intense or strong in 8 of the 11 scleroderma skin specimens, whereas it was negative or faint in 8 of the 9 normal skin specimens (P<.01). In situ hybridization demonstrated a significant increase of the number of IL-4 messenger RNA grains in scleroderma skin compared with normal skin (3.1+/-1.5 [mean+/-SD] vs 0.8+/-0.7; P<.001). A strongly positive labeling with the anti-IL-4 antibody was found in the 4 scleroderma fibroblast cultures, whereas it was negative in the 5 fibroblast control cultures (P<.05). Conclusions: Our results demonstrate that IL-4 is strongly expressed in the dermis of a large majority of patients with scleroderma and might be synthesized by scleroderma fibroblasts. We suggest that IL-4 is one of the cytokines implicated in the early steps of the fibrotic process.