Background Insulin like growth factor-I (IGF-I) is a potent differentiation and growth factor. Its level has been demonstrated to enhance in bronchoalveolar lavage fluid harvested from scleroderma patient with pulmonary fibrosis. Moreover, increased serum and tissue IGF-I levels has also been shown, in patient with morphea. On the other hand, anti-fibrotic action of octreotide has been reported in bleomycin (BLM)-induced pulmonary fibrosis model and in patients with idiopathic pulmonary fibrosis.
Objectives The aim of the present study was to research potential prophylactic and therapeutic effects of octreotide on the BLM-induced experimental scleroderma model.
Methods 60 Balb/c female mice were included in the study. They were divided 6 groups as prophylactic-early (group I [control I], group II [sham I] and group III [octreotide I]) and therapeutic-late (group IV [control II], group V [sham II] and group VI [octreotide II]) groups. Phosphate buffered saline (PBS) was injected subcutaneously and daily to shaved upper back skin in the control groups (groups I and IV). Daily subcutaneous BLM (100 mg BLM dissolved in 100 ml PBS for each mouse) was injected to shaved upper back skin for three weeks in the groups II and III, and for 6 weeks in the groups V and VI. The groups II and V were placebo (sham) groups. In addition to BLM, octreotide (100 μg/kg/day for each mouse) was injected subcutaneously to dorsal fornt of neck, for first three weeks in the group III (prophylactic 100 μg/kg), and second three weeks in the group VI (therapeutic 100 μg/kg)
Mice in the groups I, II and III (prophylactic application groups) were sacrificed at the end of third week, while groups IV, V and VI (therapeutic application groups) mice were sacrificed at the end of 6th week. Skin tissue samples were harvested for histological and real-time PCR (RT-PCR) analysis. Tissue mRNA expressions of TGF-β1, fibronectin-1, IGFBP3 and IGFBP5 were evaluated by RT-PCR.
Results Repeated BLM applications increased dermal inflammatory cell counts (Figure 1A), dermal thickness (Figure 1B) and led to dermal fibrosis at both third and 6th weeks. Moreover, mRNA expressions of TGF-β1, fibronectin-1, IFBP3 and IGFBP5 were higher in the BLM-injected sham groups compared to their controls (p<0.05 for all). On the other hand, TGF-β1, fibronectin-1, IFBP3 and IGFBP5 mRNA expressions were significantly decreased in both prophylactic and therapeutic octreotide groups compared to the own sham groups (p<0.05 for all). Similarly, in both prophylactic and therapeutic applications of octreotide decreased dermal inflammatory infiltrations and dermal thickness (Figure 1).
Conclusions The present study documents that octreotide has anti-fibrotic actions on experimentally induced dermal fibrosis. It can be suggested that IGF-I plays pathogenic roles and octreotide is candidate to research in the treatment of scleroderma.
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Disclosure of Interest None declared