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Potential Role in Fibrosis

Véronique Salmon-Ehr, MD; Hervé Serpier, MD; Béatrice Nawrocki, MS; Philippe Gillery, MD, PhD; Christine Clavel, PhD; Bernard Kalis, MD; Philippe Birembaut, MD; François-Xavier Maquart, MD, PhD

Arch Dermatol. 1996;132(7):802-806.

Abstract
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.

Arch Dermatol. 1996;132:802-806

Author Affiliations
From the Laboratoire de Recherche Biomédicale en Dermatologie (Drs Salmon-Ehr, Serpier, and Kalis), the Laboratoire de Biochimie Médicale et Biologie Moléculaire—Centre National de la Recherche Scientifique (CNRS EP 89) (Drs Gillery, Maquart, Salmon-Ehr, and Serpier), and the Institut National de la Santé et de la Recherche Médicale Unité 314 (Ms Nawrocki and Drs Clavel and Birembaut), School of Medicine, University of Reims Champagne-Ardenne, Reims, France.

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