SPONTANEOUS CYTOKINE GENE-EXPRESSION BY CULTURED SKIN FIBROBLASTS OF SYSTEMIC-SCLEROSIS - CORRELATION WITH COLLAGEN-SYNTHESIS

Objective. To investigate the spontaneous cytokine gene expression in fibroblasts from patients with diffuse cutaneous systemic sclerosis. T heir pattern of expression was correlated with the production of colla gen. Methods. Fibroblasts were obtained from skin biopsies of nine pat ients diagnosed with systemic sclerosis (mean 16 +/- 8.7 years of dise ase duration) and ten control individuals. The cytokine gene expressio n was detected by coupled reverse transcriptase polymerase chain react ion for interleukins 1 beta, 6, 8, tumour necrosis factor-alpha, and t ransforming growth factor beta. In addition, collagen synthesis was me asured by [C-14]-proline uptake in fibroblast cultures. Results. All f ibroblast samples from patients expressed the interleukin-6 gene (p = 0.04 compared with controls). Eight of the nine patients expressed int erleukin-8 (p = 0.02 compared with controls). Four of them expressed a lso transforming growth factor beta and two more weakly expressed the tumour necrosis factor-alpha gene. Only one patient showed transcripti on for the interleukin-l beta gene. In accordance with such immune act ivation, collagen synthesis was higher in fibroblasts from patients wi th systemic sclerosis (p = 0.028) as compared with normal controls. In deed, a positive correlation was found between the expression of IL-6 gene and collagen production (r(s) = 1). Conclusion. The constitutive expression of IL-6 and IL-8 genes by fibroblasts may play an important role in the perpetuation of local immune dysregulation, thus leading to a permanent fibroblast activation in patients with systemic scleros is.