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Quantification of the Immunosuppressant Tacrolimus on Dried Blood Spots Using LC-MS/MS
Published on: November 8, 2015
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Tacrolimus prevents murine cerebral malaria
Lam Quoc Bao1,2, Dang My Nhi1, Nguyen Tien Huy3
1Department of Immunogenetics, Institute of Tropical Medicine, Nagasaki University, Nagasaki, Japan.
Immunology
|August 23, 2016
Summary
Tacrolimus prevented death in mice with cerebral malaria, a severe complication of malaria. This immunosuppressant appears to work by reducing the infiltration of harmful CD8+ T cells into the brain.
Area of Science:
- Immunology
- Infectious Diseases
- Pharmacology
Background:
- Tacrolimus and mycophenolate mofetil are crucial immunosuppressants in organ transplantation.
- Tacrolimus has demonstrated in vitro efficacy against Plasmodium falciparum.
- Cerebral malaria is a severe, often fatal, complication of Plasmodium infection.
Purpose of the Study:
- To investigate the efficacy of tacrolimus and mycophenolate mofetil in a murine model of cerebral malaria.
- To elucidate the mechanism by which tacrolimus affects cerebral malaria pathology.
Main Methods:
- Utilized Plasmodium berghei ANKA-infected C57BL/6J mice to model cerebral malaria.
- Administered tacrolimus and mycophenolate mofetil to assess survival rates and disease progression.
- Analyzed brain tissue to evaluate immune cell infiltration, specifically CD8+ T cells.
Main Results:
- Tacrolimus significantly prevented mortality from cerebral malaria but not from high parasitemia or anemia.
- Mycophenolate mofetil treatment resulted in increased mortality and earlier death from cerebral malaria compared to tacrolimus.
- Tacrolimus treatment attenuated the infiltration of mononuclear cells, including CD8+ T cells, into the brain.
Conclusions:
- Tacrolimus demonstrates a protective effect against cerebral malaria in mice.
- The mechanism of protection involves the inhibition of pathogenic CD8+ T cell infiltration into the brain.
- Tacrolimus may be a potential therapeutic agent for cerebral malaria, warranting further investigation.
