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Leukocyte mobilization into the blood stream in response to cytokines is well documented.51,52 It has been shown that IL-4 is an essential differentiation factor for Th2 cells.66 Oxidative stress might induce IL-4 production by mast cells and basophils and direct the Th2 cell differentiation.67 IL-4 may be considered as a pro-oxidative cytokine that can increase the oxidative potential of target cells.68 IL-4 induced the generation of ROS such as superoxide anion and hydrogen peroxide.69 This imbalance between oxidants and antioxidants favors skewing of the Th2 immune response while suppressing Th1 differentiation.70 The results of present study seem to suggest that the aspartame metabolite methanol or formaldehyde may be involved in inducing oxidative stress in serum and in changes of cytokine secretion where Th1 cytokines are down-regulated and Th2 cytokines are up-regulated, which may alter cell and humoral immunity

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In the cell experiments, metformin was used at a concentration of 1 mM, simvastatin was used at 2 µM, and when combined, the concentrations were 0.5 mM for metformin and 1 µM for simvastatin