Therapeutical effects of FK506 on BXSB mice with lupus nephritis and its mechanism

LU Jie; LIU Huafeng; TANG Deshen; LIANG Dong; CHEN Xiaowen

Abstract：To study the therapeutical effects of FK506 on BXSB mice with lupus nephritis (LN) and primarily evaluate the mechanism. With six 12-weeek-old male C57BL/6 mice acted as normal control group, twelve 12-weeek-old male LN BXSB mice were randomly di-vided into treated and untreated LN groups. The treated group was given 2 mg/kg FKS06 by intraperitoneal injection every other day for eight weeks. While the untreated group and control group were given 0.2 ml saline by the same route and interval. All mice were sacrificed after 8 weeks. The pathological feature was observed by PASM staining; IgG deposition was detected by direct immunofluorescence; sera levels of anti-ds-DNA antibody and IL-18 were measured by ELISA; the renal expression of IL-18mRNA was detected by RT-PCR;IL-18 protein expression in kidney was determined by immunohistochemistry. Compared with the untreated group, the pathological feature were improved, the deposition of IgG was reduced, the serum expressions of anti-dsDN A antibody and IL-18 were decreased, and the renal expression of IL -18 protein and mRNA were all reduced significantly in treated group. In the light of these results, we deduced that inhibiting IL-18 mRNA expression maybe one of the mechanisms to explain the therapeutical effects of FKS06 on LN BXSB mice.