Modulation of cerebral malaria by fasudil and other immune-modifying compounds.
Malaria continues to cause millions of deaths annually. No specific effective treatment has yet been found for cerebral malaria, one of the most severe complications of the disease. The pathology of cerebral malaria is considered to be primarily immunological. We examined a number of compounds with known effects on the immune system, in a murine model of cerebral malaria. Of the compounds tested, only fasudil and curcumin had significant effects on the progression of the disease. Although neither drug caused a reduction in parasitemia, survival of the treated mice was significantly increased, and the development of cerebral malaria was either delayed or prevented. Our results support the hypothesis that an immunomodulator efficient in preventing CM should be administered together with anti-plasmodial drugs to prevent severe malaria disease; curcumin and fasudil should be further investigated to determine efficiency and feasibility of treatment.
Waknine-Grinberg
Judith H
JH
Department of Microbiology and Molecular Genetics, The Hebrew University of Jerusalem, Jerusalem 91120, Israel.
McQuillan
James A
JA
Hunt
Nicholas
N
Ginsburg
Hagai
H
Golenser
Jacob
J
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000818:Animals; D003474:Curcumin / Q000627:therapeutic use; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D005260:Female; D007155:Immunologic Factors / Q000627:therapeutic use*; D016779:Malaria, Cerebral / Q000188:drug therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D018512:Parasitemia / Q000188:drug therapy; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D013047:Specific Pathogen-Free Organisms; D014665:Vasodilator Agents / Q000627:therapeutic use*; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors
D004791:Enzyme Inhibitors; D007155:Immunologic Factors; D047428:Protein Kinase Inhibitors; D014665:Vasodilator Agents; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D054460:rho-Associated Kinases; D003474:Curcumin; C049347:fasudil