Artesunate protects immunosuppression mice induced by glucocorticoids via enhancing pro-inflammatory cytokines release and bacterial clearance

Glucocorticoids are commonly used in clinic, but the immunosuppression seriously hinders their usage. Herein, immunomodulatory effect of artesunate (AS) on hydrocortisone (HC)-induced immunosuppression was investigated. HC-induced immunosuppression mice (HC mice) were established by intramuscular administration with HC (20 mg/kg) once a day for 5 consecutive days. The results showed HC mice challenged with Escherichia coli on the sixth day presented a lower ability to clear bacteria, decreased TNF-alpha in blood, decreased spleen index and thymus index. Significantly, AS (20 mg/kg) treatment not only enhanced the ability of HC mice to clear bacteria, but also increased spleen index, the levels of pro-inflammatory cytokines from 78.7 + 12.1 ng/ml (TNF-alpha) and 48.7 + 8.6 pg/ml (IL-6) to 174.0 + 90.5 ng/ml and 783.3 + 90.5 pg/ml, number of white blood cells in blood, and sIgA in colon. Subsequently, HC-induced immunosuppression peritoneal macrophages model (HC cells) was established via addition of HC (0.5 mu g/ml) for 0.5 h, and then LPS (100 ng/ml) was added to clarify the functional status of the cells. The results showed HC inhibited TNF-alpha and IL-6 mRNA expressions and their release, but AS (2.5 mu g/ml) could increase TNF-alpha and IL-6 mRNA expressions and their release. AS inhibited GILZ mRNA up-regulated by HC and increases TLR4/NF-kappa B p65 expressions down-regulated by HC. Our findings revealed that AS's effect is closely related to the improvement of the TLR4/NF-kappa B signal transduction pathway via inhibiting the up-regulation of GILZ mRNA, demonstrating AS does possess immunomodulatory effects and is worth further investigation in the future.

Automated summary

The study demonstrated that artesunate has immunomodulatory effects on hydrocortisone-induced immunosuppression, enhancing bacterial clearance ability and increasing inflammatory response. Artesunate's effect is related to the improvement of the TLR4/NF-kappa B signal transduction pathway by inhibiting the upregulation of GILZ mRNA. Further investigation into the immunomodulatory effects of artesunate is warranted.