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.


METHODS
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.
Salmon-Ehr
V
V
Laboratoire de Recherche Biomédicale en Dermatologie, School of Medicine, University of Reims Champagne-Ardenne, France.
Serpier
H
H
Nawrocki
B
B
Gillery
P
P
Clavel
C
C
Kalis
B
B
Birembaut
P
P
Maquart
F X
FX
D000328:Adult; D000368:Aged; D002478:Cells, Cultured; D005260:Female; D005347:Fibroblasts / Q000378:metabolism*; D005355:Fibrosis; D006801:Humans; D015847:Interleukin-4 / Q000096:biosynthesis*; D008297:Male; D008875:Middle Aged; D012595:Scleroderma, Systemic / Q000378:metabolism* / Q000473:pathology; D012867:Skin / Q000378:metabolism / Q000473:pathology*
D015847:Interleukin-4