ABSTRACT
Background: Management of multiple sclerosis [MS] is based on the usage of immunosuppressive and immune-modulating medications. Cytokines play an important role in the pathogenesis of MS
Objective: To evaluate the effects of rapamycin on the concentrations of Th1/Th2/Th17 serum cytokines in patients with MS
Methods: Six patients with relapsing remitting MS as a case group and 6 healthy individuals as a control group were enrolled. The patients have been receiving 2 mg rapamycin daily for 6 months. The individuals in control group received nothing during 6 months of the experiment. Enzyme linked immunosorbent assay [Simultaneous Multi-Analyte ELISA] technique was used for determination of serum concentrations of IL-2, IL-4, IL-5, IL-6, IL-10, IL-12, IL-13, IL-17, IFN-gamma, TNF-alpha, G-CSF and TGF-beta before and after therapy with rapamycin
Results: The mean absorbance of 10 out of the 12 studied cytokines showed reduction after the therapy with rapamycin including IL-2, IL-4, IL-5, IL-6, IL-10, IL-12, IL-13, IL-17, IFN-gamma and TNF-alpha. The only statistically significant reduction was observed in the absorbance of IFN-gamma [p=0.028]. Two cytokines illustrated increase in the patients sera after the therapy, including G-CSF and TGF-beta, but only increase in TGF-beta was statistically significant [p=0.046]. None of the studied cytokines in the control group varied significantly after 6 months
Conclusion: Based on the findings of this study, rapamycin has some immunosuppressive effects, such as decreasing IFN-gamma, which can improve the quality of life of the patients with multiple sclerosis. Also the increased level of TGF-beta may also have benefits on the disease, which needs further clinical studies
ABSTRACT
Iron is an essential trace element in cell proliferation. Several investigations demonstrate that iron deprivation inhibits cell proliferation. However, the impact of iron on telomerase activity of activated lymphocytes remains unexplained to date. In this study, the effect of iron on the proliferation and telomerase activity of lymphocytes stimulated by phytohemagglutinin [PHA] were investigated. Iron loading was performed by incubating peripheral blood mononuclear cells in 500 micro M FeSO[4].7H[2]O for 24 h and iron chelation was done by exposing cells to desferrioxamine, a potent iron chelator. The effects of silymarin, a flavonoid with both antioxidant and iron chelating activities, on the proliferation and telomerase activity of PHA-activated lymphocytes were also compared with desferrioxamine. Proliferation and telomerase activity were assessed using BrdU incorporation assay and Telomeric Repeat Amplification Protocol [TRAP], respectively. The proliferations of lymphocytes were significantly inhibited by 10 and 20 micro g/ml desferrioxamine in a dose dependent manner, while iron loading recovered suppressed cell proliferation to the normal level. Silymarin at 20 micro g/ml significantly increased the proliferation of lymphocytes in both normal and iron-treated conditions. Telomerase activity of lymphocytes was markedly increased by iron treatment and suppressed by desferrioxamine. Conversely, iron treatment had no effect on the telomerase activity of lymphocytes incubated with silymarin. Iron plays a significant role in the proliferation and telomerase activity of lymphocytes. The effects of silymarin on the proliferation and telomerase activity of lymphocytes were completely different from those of desferrioxamine, suggesting that the immunomodulatory effect of silymarin is probably not associated with its iron chelating activity