Search

Background Scleroderma is a chronic inflammatory disease characterized by widespread fibrosis of the skin and the internal organs. Ghrelin is a polypeptide hormone produced by various tissues and inflammatory cells. In experimental studies, ghrelin has been shown to have anti-inflammatory and antioxidant effects, in addition to its metabolic actions. Aim To evaluate the potential preventive effects of ghrelin on a mouse model of bleomycin ( BLM)-induced scleroderma. Methods This study involved five groups of BALB/c mice ( n = 7 in each group). Mice in the control group received 100 μL/day of phosphate-buffered saline ( PBS) subcutaneously, while the other four groups were given 100 μg/day of BLM (dissolved in 100 μL PBS) subcutaneously. Three of the BLM-treated groups received intraperitoneal doses (10 ng/kg/day) of acylated, nonacylated or total ghrelin. Animals were killed at the end of the fourth week, and blood and tissue samples were collected for further analysis. Dermal thickness, serum levels of transforming growth factor-β1, numbers of inflammatory cells on the dermal layer and numbers of α-smooth muscle actin-positive cells were determined. Results BLM increased dermal thickness, numbers of inflammatory cells on the dermal layer and activity of the myofibroblastic cells. Application of acylated, nonacylated and total ghrelin decreased the infiltration of inflammatory cells and the activity of the myofibroblastic cells, and reduced dermal fibrosis. Conclusions Based on these results, it appears that ghrelin has an antifibrotic action, in addition to the anti-inflammatory and antioxidant effects that have been documented previously. The pathogenic and therapeutic roles of ghrelin in scleroderma should be evaluated by further studies. [ABSTRACT FROM AUTHOR]

Summary Background. T lymphocytes induce the transformation of fibroblasts into myofibroblasts, the main mediators of fibrogenesis. The inosine 5′-monophosphate dehydrogenase inhibitor mycophenolate mofetil (MMF) and the anti-CD25 monoclonal antibody daclizumab (DCZ) have been reported to suppress the proliferation of T lymphocytes. Aim. To evaluate the preventive effects of MMF and DCZ in early stages of bleomycin (BLM)-induced scleroderma. Methods. This study involved five groups of Balb/c mice ( n = 10 per group). Mice in four of the groups were injected subcutaneously (SC) with BLM [100 μg/day in 100 μL phosphate-buffered saline (PBS)] for 4 weeks; the remaining (control) group received only 100 μL PBS. Three of the BLM-treated groups also received either intraperitoneal MMF 50 or 150 mg/kg/day, or SC DCZ 100 μg/week. At the end of the fourth week, all mice were killed, and blood and tissue samples were obtained for further analysis. Results. In the BLM-treated group, increases were seen in inflammatory-cell infiltration, α-smooth muscle actin-positive (α-SMA+) fibroblastic cell count, tissue hydroxyproline content, and dermal thickness. Dermal fibrosis was histopathologically prominent. In BLM-treated mice also given MMF or DCZ, inflammatory-cell infiltration, tissue hydroxyproline content and dermal thickness were decreased. In the MMF groups, decreases were also noted in α-SMA+ fibroblastic cell count. Conclusion. In this BLM-induced dermal fibrosis model, MMF and DCZ treatments prevented the development of dermal fibrosis. Further studies are needed to evaluate whether targeting T lymphocytes is effective in resolving pre-existing fibrosis in human scleroderma. [ABSTRACT FROM AUTHOR]