EXPRESSION OF INTERLEUKIN-4 IN SCLERODERMA SKIN SPECIMENS AND SCLERODERMA FIBROBLAST-CULTURES - POTENTIAL ROLE IN FIBROSIS

Background: Scleroderma (systemic sclerosis) is a fibrotic disease cha racterized by an uncontrolled tissular accumulation of collagen. Sever al cytokines have been implicated in the fibroblast activation leading to fibrosis. For instance, we have previously demonstrated that inter leukin-4 (IL-4) is a potent activator of collagen synthesis in fibrobl ast cultures. In this study, using immunocytochemical methods and in s itu hybridization, we investigated the expression of IL-4 in normal an d scleroderma skin and fibroblast cultures. Observations: Immunocytoch emical studies with anti-IL-4 antibody were performed on biopsy specim ens from 9 patients with normal skin and 11 patients with scleroderma. The label was intense or strong in 8 of the 11 scleroderma skin speci mens, whereas it was negative or faint in 8 of the 9 normal skin speci mens (P<.01). In situ hybridization demonstrated a significant increas e of the number of IL-4 messenger RNA grains in scleroderma skin compa red with normal skin (3.1+/-1.5 [mean+/-SD] vs 0.8+/-0.7; P<.001). A s trongly positive labeling with the anti-IL-4 antibody was found in the 4 scleroderma fibroblast cultures, whereas it was negative in the 5 f ibroblast control cultures (P<.05). Conclusions: Our results demonstra te that IL-4 is strongly expressed in the dermis of a large majority o f patients with scleroderma and might be synthesized by scleroderma fi broblasts. We suggest that IL-4 is one of the cytokines implicated in the early steps of the fibrotic process.