The Effects of Arsenic Trioxide on Expression of IFN-γ， IL-4 and Th Balance in MRL/lpr Mice

Abstract: To investigate the effects of arsenic trioxide (ATO) on the expression of IFN-γ， IL-4 and Th balance in MRL/lpr mice in both early and later stage of the disease， young (3-month-old) and old (5-month-old) MRL/lpr mice were chosen for such experiment， each age group was then separated in 3 different sub-groups. The 3 sub-groups of both age groups received arsenic trioxide [ATO， 0.4 mg/(kg·d)]， cyclophosphamide [CYC， 50 mg/(kg·qw)] and sodium chloride (NS， volume weight-determined) abdominal injection respectively for 2 months. Afterwards， serum levels of IFN-γ， and IL-4 were assayed using the mouse cytokines ELISA kit. The rates of the CD3+ (T) cells， CD3+CD4+ (Th) cells and the CD3⁺CD4⁺IFN-γ+IL-4 ^- (Th1) cells CD3+CD4+IL-4⁺IFN-γ ^- (Th2) cells were detected using single-cell measurement of intracellular cytokines by flow cytometry. Results showed that: ① The production of anti-dsDNA autoantibody was markedly decreased in both of the ATO-treated mice (the young P=0.012， the old P=0.000)， while it was dramatically increased in the NS groups (the young P=0.002， the old P=0.002). ② Compared to NS-treated mice， the levels of IFN-γ， IL-4 was dramatically lower in ATO-treated mice (P<0.05). ③ The ATO-treated mice had significantly fewer CD3⁺ cells， Th1 and Th2 cells than NS-treated mice (P<0.05). ATO-treated young mice had significantly fewer CD3⁺CD4⁺ cells than Ns-treated young mice (P=0.007). ④ Th1/Th2 ratio in NS-treated old mice was greater than the young ones (P=0.003)， while there was no significant difference between the two age groups of ATO-treated mice. It was concluded that， ATO can reduce the production of anti-dsDNA autoantibody in both early and later stages of the disease， inhibit the activation and proliferation of both T cells and Th subsets in MRL/lpr mice， decrease the expression of IFN-γ and IL-4， and partly adjust the shifting of 5-month-old MRL/lpr mice to Th1.

CSTR: 32200.14.cjcb.2008.04.0020