Expression of Interleukin-4 in Scleroderma Skin Specimens and Scleroderma Fibroblast Cultures
Posted Mar 09 2011 2:29am
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.
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.
Arch Dermatol. 1996;132:802-806