Dihydroartemisinin attenuated the symptoms of mice model of systemic lupus erythematosus by restoring the Treg/Th17 balance

Abstract

The Treg/Th17 imbalance is associated with the development of systemic lupus erythematosus (SLE). Dihydroartemisinin (DHA), a semi-synthetic derivative of artemisinin, is isolated from the traditional Chinese herb Artemisia annua Artemisia annua L. This study aims to evaluate the effects of DHA alone or in combination with prednisone in immunodeficiency of SLE. In vivo, the therapeutical effect of DHA alone or in combination with prednisone was assessed in the pristane-induced SLE mouse model. Then, the level of serum antibodies, creatinine (Cre), blood urea nitrogen (BUN), urine protein, kidney histopathology, interleukin (IL)-17, IL-6, transforming growth factor (TGF)-β, the expression of RORγt and Foxp3, the percentages of Treg and Th17 in peripheral blood and spleen were assayed. In vitro, the mouse spleen lymphocytes were separated and treated with DHA alone or DHA in combination with prednisone. Then the percentages of Treg and Th17, the concentration of IL-17, IL-6, TGF-β, and the expression of RORγt and Foxp3 were assayed. It was shown that DHA alone or in combination with prednisone treatment significantly alleviated the manifestations of pristane-induced SLE mice, suppressed inflammation and restored the Treg/Th17 balance. DHA alone or in combination with prednisone significantly inhibited Th17 cell differentiation while induced Treg cell differentiation in vitro. DHA alone or in combination with prednisone also reduced the transcription of RORγt and increased Foxp3 in lymphocytes, as well as IL-17 and TGF-β levels. Our data indicated that DHA can produce synergistic effect with prednisone to attenuate the symptoms of SLE by restoring Treg/Th17 balance.