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Abstract
The T‐helper 1/T‐helper 2 (Th1/Th2) cell balance was examined in 6‐month‐old New Zealand black/white F1 (B/WF1) mice treated with an immunosuppressive agent, FK506. The survival rate of mice treated with 10 mg/kg/day of FK506 was 7/8, while that of those treated with 2.5 mg/kg/day was 5/8, and 4/8 after treatment for 8 weeks with placebo. Proteinuria, which was already positive in all mice before the treatment, in the seven of eight mice treated with 10 mg/kg/day remained mildly positive (≤1+), while seven of eight mice treated with 2.5 mg/kg/day and six of eight mice treated with the placebo showed severe proteinuria (≥2+). Pathological changes in the kidneys of mice treated with 10 mg/kg/day of FK506 were less severe than in mice treated with the placebo or 2.5 mg/kg/day of FK506. Expression of mRNA was unchanged for all cytokines determined in the groups treated with 2.5 mg/kg/day of FK506 or placebo. In contrast, expression of mRNA for interleukin (IL)‐2, and interferon (IFN)‐γ was suppressed, while that for IL‐4 and IL‐10 was not suppressed in the group treated with 10 mg/kg of FK506. The serum levels of IgG‐class anti‐DNA antibodies, which had been elevated before the treatment, were suppressed — especially in the IgG2a subclass — and the deposition of IgG2a and IgG2b in the glomeruli was reduced in the group treated with 10 mg/kg/day of FK506 compared with the other groups. These findings suggest that an improvement in the lupus nephritis of 6‐month‐old B/WF1 mice induced by FK506 might be associated with a predominant inhibition of Th1 cytokine.
