Stem Cell Mobilization with G-CSF and Cyclophosphamide Ameliorated Collagen-Induced Arthritis in Wistar Rats

Abstract

Background and Objective: Rheumatoid arthritis is an inflammatory autoimmune disorder which affects multiple joints and causes cartilage erosion. It's treatment depends on the systemic use of anti-inflammatory and immunosuppressive drugs. The aim of this study was to test effect of combination of Granulocyte-Colony Stimulating Factor (G-CSF), cyclophosphamide (CTX) and Bone Marrow (BM) cells on Collagen Induced Arthritis (CIA) in Wistar rats. Materials and Methods: Collagen Induced Arthritis (CIA) was induced in Wistar rats by subcutaneous (s.c.) injection of 200 and 100 mu L/rat of collagen II at tail base in on days 0 and 12, respectively. Then, rats were treated with either intravenous injection of fresh Bone Marrow (BM) cells (5 x 10(6)) or s.c. injection of G-CSF (5 Lig for s.c. for 5 consecutive days) in presence or absence of a single intraperitoneal injection of cyclophosphamide (4 mu g/rat). Inflamed paws, x-ray and histopathological examination were assessed during the experiment. Serum levels of IL-4, IL-8 and TNF-alpha were also measured. Results: All treatments decreased inflammation in the paws as reflected by decreased paw thickness in fore and hind limbs and confirmed by x-ray and histological examination.Of note, the anti-CIA effects after treatment with CTX plus G-CSF were higher than of CTX plus BM cells and other treatment modalities (CTX or BM alone). Interestingly, all treatment modalities induced decreases in levels of IL-4, IL-8 and INF-alpha. Among them, CTX/G-CSF showed the highest inhibitory effect on TNF-alpha. Conclusion: Treatment of CIA rats with the combination of G-CSF and CTX induces potential anti-arthritic effect. This anti-arthritic effect is through down regulating the elevated levels of IL-4, IL-8 and TNF-alpha cytokines.