Malaria mimicry with tumor necrosis factor. Contrasts between species of murine malaria and Plasmodium falciparum.
Because Plasmodium berghei ANKA induces cerebral malaria and P. vinckei does not, the former has often been studied as a model for human falciparum malaria. It lacks, however, many of the systemic changes seen in the human disease. Because both of these murine models and the human disease have now been defined in terms of excess tumor necrosis factor (TNF) production, the authors have more closely examined the two murine models in this light to see which provides the better overall model for falciparum malaria. Administering TNF to malaria-infected mice did not cause cerebral symptoms nor breakdown of the blood-brain barrier, which is the hallmark of P. berghei ANKA cerebral malaria and is generally absent in human cerebral malaria. Tumor necrosis factor did, however, induce hypoglycemia and liver injury, pathology that is seen in terminal P. vinckei and falciparum malaria, but is absent in terminal P. berghei ANKA malaria. Plasma TNF and interleukin-6 (IL-6) also were found to be consistently higher in infections caused by P. vinckei than in those caused by P. berghei ANKA. The pathology of P. vinckei malaria is thus consistent with raised systemic levels of TNF and other cytokines, as is falciparum malaria. The authors therefore conclude that P. vinckei malaria, although lacking a cerebral component, is the better model for the human disease.
Clark
I A
IA
Division of Biochemistry and Molecular Biology, School of Life Sciences, Australian National University, Canberra.
MacMicking
J D
JD
Gray
K M
KM
Rockett
K A
KA
Cowden
W B
WB
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001812:Blood-Brain Barrier / Q000187:drug effects; D004195:Disease Models, Animal; D005260:Female; D015850:Interleukin-6 / Q000097:blood; D008109:Liver Diseases, Parasitic / Q000473:pathology; D016779:Malaria, Cerebral / Q000097:blood / Q000139:chemically induced* / Q000469:parasitology; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D010961:Plasmodium; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000494:pharmacology*
D001786:Blood Glucose; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha