BASIC FIBROBLAST GROWTH FACTOR IN SYSTEMIC SCLEROSIS

Background: Biochemical and pathological investigations demonstrated that endothelial cell injury occurs in the early stages of systemic sclerosis. Endothelial cells, on the other hand, contribute to the inflammatory processes by producing and secreting a number of cytokines, including bFGF, which can modulate fibroblast properties. Thus, endothelial cell and fibroblast dysfunction may be linked through the paracrine activity of soluble endothelial cell products. Basic fibroblast growth factor (bFGF) is a cytoplasmic polypeptide growth regulator that induces endothelial cell and fibroblast proliferation.Objectives: To investigate circulating levels of bFGF in patients with systemic sclerosis in relation to acute phase reactants and disease duration.Methods: Eleven patients with diffuse type systemic sclerosis (male/female: 2/9, mean age: 37.8, min-max: 23-53), and 10 healthy controls (male/female: 4/6, mean age: 32,3, min-max: 19-44) were enrolled in the study. Mean duration of symptoms is 11.8 years (min-max: 4-24). Blood sampling were performed in the morning after 15 hours of fasting. bFGF levels were measured using a commercially available kit (Quantikine Human bFGF Immunoassay, R&D Systems Inc., Minneapolis, USA). Minimum detectable dose of FGF basic in this assay is typically less than 3 pg/mL.Results: bFGF levels were 37.48 pg/mL (11.7-112.2) and 22.68 pg/mL (12.4-42.5) for patients with systemic sclerosis and for healthy controls, respectively. However, this difference could not reach to a statistically significant level (p>0.05, Mann-Whitney U test). Moreover, there was no correlation between bFGF levels and acute phase reactants (erythrocyte sedimentation rate and C-reactive protein) and the duration of symptoms.Conclusion: Although the etiopathogenesis of systemic sclerosis is unknown, fibroblast overactivity has been proposed depending on the histopathological observations which demonstrated fibrotic changes in the skin and many other organ systems. Increased collagen type I and type III synthesis in scleroderma skin fibroblasts was previously demonstrated. Elevated collagen synthesis is accompanied by elevated levels of mRNA for these proteins. However, although bFGF was shown to inhibit collagen gene expression in several cell types, it diminished collagen expression on mRNA and protein levels in normal and scleroderma fibroblasts in similar manner. Moreover, collagen mRNA expression in scleroderma fibroblasts was shown to be independent of bFGF signal transduction pathway. Similarly, other in-vitro studies showed a decreased responsiveness of scleroderma fibroblasts to various growth factors, including bFGF. In a subgroup of scleroderma patients (31/74 of patients) detectable levels of bFGF was shown while the bFGF was undetectable in the serum of normal persons. However, our results could not demonstrate a statistically significant difference between patients with scleroderma and healthy subject, and moreover, failed to show a correlation between disease activity or disease duration and bFGF levels. Therefore, bFGF does not seem to be a good indicator of disease activity in scleroderma patients. Prospective longitudinal data obtained by serial measurements of bFGF during the disease course in a larger group of patients would give better information in this research area.Citation: , volume , supplement , year 2002, page Session: Scleroderma and related syndromes 2