Dihydroartemisinin regulates the immune system by promotion of CD8+ T lymphocytes and suppression of B cell responses

Sci China Life Sci. 2020 May;63(5):737-749. doi: 10.1007/s11427-019-9550-4. Epub 2019 Jul 8.


Artemisia annua is an anti-fever herbal medicine first described in traditional Chinese medicine 1,000 years ago. Artemisinin, the extract of A. annua, and its derivatives (dihydroartemisinin (DHA), artemether, and artesunate) have been used for the treatment of malaria with substantial efficacy. Recently, DHA has also been tested for the treatment of lupus erythematosus, indicating that it may function to balance the immune response in immunocompromised individuals. In the present study, the regulatory effect of artemisinin on the murine immune system was systematically investigated in mice infected with two different protozoan parasites (Toxoplasma gondii and Plasmodium berghei). Our results revealed that the mouse spleen index significantly increased (spleen enlargement) in the healthy mice after DHA administration primarily due to the generation of an extra number of lymphocytes and CD8+ T lymphocytes in both the spleen and circulation. DHA could increase the proportion of T helper cells and CD8+ T cells, as well as decrease the number of splenic and circulatory B cells. Further, DHA could reduce the production of proinflammatory cytokines. Our study revealed that apart from their anti-parasitic activity, artemisinin and its derivatives can also actively modulate the immune system to directly benefit the host.

Keywords: Plasmodium berghei; Toxoplasma gondii; artemisinin; cytokine; immune cells; immunomodulation.

MeSH terms

  • Animals
  • Antimalarials / chemistry*
  • Antimalarials / metabolism
  • Antimalarials / pharmacokinetics
  • Artemisinins / chemistry*
  • Artemisinins / metabolism
  • Artemisinins / pharmacology
  • B-Lymphocytes / drug effects
  • CD8-Positive T-Lymphocytes / drug effects
  • Cytokines / metabolism
  • Drugs, Chinese Herbal / chemistry*
  • Drugs, Chinese Herbal / metabolism
  • Drugs, Chinese Herbal / pharmacology
  • Female
  • Humans
  • Immune System / drug effects*
  • Immunomodulation / drug effects
  • Malaria / drug therapy*
  • Mice
  • Mice, Inbred BALB C
  • Plasmodium berghei / drug effects
  • Spleen / drug effects
  • T-Lymphocytes, Regulatory / drug effects
  • Toxoplasma / drug effects


  • Antimalarials
  • Artemisinins
  • Cytokines
  • Drugs, Chinese Herbal
  • artenimol