Efficacy of octreotide treatment on bleomycin induced experimental scleroderma model

Scleroderma is a chronic inflammatory disease characterized by skin and various internal organ fibrosis. The pathogenesis of the disease is not clearly understood but fibrosis is formed by excessive synthesis and deposition of collagen and extracellular matrix molecules. Octreotide is the analog of somatostatin which regulates growth hormone (GH) secretion. GH increases the production of insülin like growth factor-1 (IGF-1) from the liver. Various effects of GH is maintained by IGF-1. IGF-1 is a strong growth and a differantiation factor. IGF-1 levels in bronchoalveolar fluid is shown to be increased in scleroderma patients with pulmonary fibrosis. Similarly, tissue and serum IGF-1 levels are found to be high in morfea patients. The anti-fibrotic effect of octreotide is shown in patients with idiopathic pulmonary fibrosis and the model of bleomycin induced pulmonary fibrosis. The aim of this study is to determine the preventive and therapeutic effects of octreotide on bleomycin-induced experimental scleroderma model. 60 Balb/c female mice were included in this study. They were divided into 6 equal groups such as early phase groups (group I [control], II [sham-1], III [prophlactic octreotide]) and late phase groups (group IV [control], V [sham-2], VI [therapeutic octreotide]). To the control mice (group I and group IV), subcutaneous (sc) daily saline buffered with phosphate (PBS) was administered to the shaved area. 1 mg BLM dissolving in 1 mL PBS was administered daily for 3 weeks to the rats in groups II and III and for 6 weeks to mice in groups V and VI sc at a dose 100 μL (100 μg). In addition to the BLM, rats in Group III (prophylactic octreotide) starting from the first day of the study and group VI (therapeutic octreotide) from day 21, received sc octreotide at a dose of 100 μg/kg until the end of study. Mice in group I, II and III were sacrified on third week and those in group IV, Vand VI on sixth week and tissue samples were removed for analyzes. Tissue TGF-β1, IGFBP-3 and IGFBP-5 mRNA expressions were determined by RT-PCR method. Administrations of bleomycin caused an increase in dermal inflammatory cell infiltration, dermal fibrosis and dermal thickening. Similarly, mRNA expressions of TGF-β1, IGFBP-3 and IGFBP-5 are increased in BLM administered placebo group compared to control group. mRNA expression of TGF-β1 is decreased in both prophlactic and therapeutic octreotide group compared to placebo. However, mRNA expressions of IGFBP-3 and IGFBP-5 are markedly decreased only in therapeutic octreotide group. On the other hand, histopathologically dermal necroinflammation is decreased in both prophylactic and therapeutic groups by octreotide. In conclusion, it can be suggested that IGF-1 contributes to dermal fibrosis and octreotide has a potential anti-fibrotic effect. Keywords: Experimantal scleroderma, Insulin like growth factor-1, Octreotide