To evaluated the effect and mechanism of
leflunomide (LEF) in murine model of collage-induced
arthritis (CIA) on modulating the balance of Th17/Treg cells. DBA mice were divided into: control, CIA, CIA + LEF and CIA +
Ibuprofen group. After 14 days immunization with bovine
type II collagen (CII), except control group, mice were orally administered saline (CIA group), LEF or
ibuprofen daily for 14 days. The severity of
arthritis joint was assessed by using
arthritis score. The numbers of CD3 + CD4 +
interleukin 17 (IL-17) + Th17 cells and CD4 + CD25 + Foxp3+ Tregs were determined by flow cytometry, the expression of ROR-γt, Foxp3 and
IL-21 mRNA in spleen were quantified by RT-PCR and
IL-17,
IL-21 and
transforming growth factor β (TGF-β) level in serum was measured by ELISA. In comparison with CIA group, CIA + LEF and CIA +
Ibuprofen group reduced the disease severity obviously (p < 0.05).
Leflunomide reduced Th17 cells, the expression of ROR-γt and
IL-21 mRNA (p < 0.05) and the levels of
IL-17 and
IL-21 in serum. In addition,
Ibuprofen but not LEF has effect on Treg cells number, Foxp3
mRNA expression and TGF-β secretion. These results indicate that LEF effect on the balance od Th17/Treg through suppressing Th17 cells, but not stimulating Treg cells.
Leflunomide may act as a potential
immunomodulator for the treatment of
rheumatoid arthritis (RA).