Journal
EUROPEAN JOURNAL OF PHARMACOLOGY
Volume 890, Issue -, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.ejphar.2020.173630
Keywords
Artesunate; Glucocorticoids; Immunosuppression; Pro-inflammatory cytokines; GILZ; NF-kappa B p65
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Funding
- National Natural Science Foundation of China-Guizhou Provincial People's Government Joint Fund Project [NSFC-U1812403-4-1]
- National Natural Science Foundation of China [NSFC- 81872914, 82073902]
- fourth batch of Thousand People Innovation and Entrepreneurship Talents Fund in Guizhou Province
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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.
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.
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