Role of eicosanoids in the pathogenesis of murine cerebral malaria.
Because microvascular damage is a common feature of cerebral malaria, we have examined the role eicosanoid metabolites (prostaglandins and leukotrienes) in experimental cerebral malaria. Eighty ICR mice were infected with Plasmodium berghei ANKA, with 40 uninfected mice as controls. Half of the infected mice were treated on days 4 and 5 with aspirin, a prostaglandin synthesis inhibitor. Infected mice started to die of cerebral malaria on day 6, and by day 17, all infected mice died. In contrast, all infected mice treated with aspirin died by day 12. Infected mice had increased phospholipase A2 mRNA expression in the spleen and cyclooxygenase 1 (COX1) and COX2 expression in the brain. At the peak of cerebral malaria, infected mice had higher serum leukotriene B4 levels than control mice, and aspirin-treated infected mice had higher serum leukotriene B4 levels than untreated infected mice. These results suggest that prostaglandins are protective whereas leukotrienes are detrimental in cerebral malaria.
Xiao
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Division of Parasitic Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia 30341-3724, USA.
Patterson
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PS
Yang
C
C
Lal
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D000818:Animals; D001241:Aspirin / Q000008:administration & dosage / Q000494:pharmacology; D001921:Brain / Q000201:enzymology; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D005260:Female; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D007975:Leukotriene B4 / Q000097:blood; D015289:Leukotrienes / Q000502:physiology*; D008084:Lipoxygenase / Q000235:genetics / Q000378:metabolism; D016779:Malaria, Cerebral / Q000469:parasitology / Q000503:physiopathology*; D008565:Membrane Proteins; D051379:Mice; D008813:Mice, Inbred ICR; D018512:Parasitemia; D010741:Phospholipases A / Q000235:genetics / Q000378:metabolism; D054467:Phospholipases A2; D010962:Plasmodium berghei / Q000302:isolation & purification; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics / Q000378:metabolism; D011453:Prostaglandins / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013154:Spleen / Q000201:enzymology
D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D015289:Leukotrienes; D008565:Membrane Proteins; D011453:Prostaglandins; D007975:Leukotriene B4; D008084:Lipoxygenase; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; C496512:Ptgs1 protein, mouse; D010741:Phospholipases A; D054467:Phospholipases A2; D001241:Aspirin