Uric acid is a mediator of the Plasmodium falciparum-induced inflammatory response.
BACKGROUND
Malaria triggers a high inflammatory response in the host that mediates most of the associated pathologies and contributes to death. The identification of pro-inflammatory molecules derived from Plasmodium is essential to understand the mechanisms of pathogenesis and to develop targeted interventions. Uric acid derived from hypoxanthine accumulated in infected erythrocytes has been recently proposed as a mediator of inflammation in rodent malaria.


RESULTS
We found that human erythrocytes infected with Plasmodium falciparum gradually accumulate hypoxanthine in their late stages of development. To analyze the role of hypoxanthine-derived uric acid induced by P. falciparum on the inflammatory cytokine response from human blood mononuclear cells, cultures were treated with allopurinol, to inhibit uric acid formation from hypoxanthine, or with uricase, to degrade uric acid. Both treatments significantly reduce the secretion of TNF, IL-6, IL-1beta and IL-10 from human cells.


CONCLUSIONS
Uric acid is a major contributor of the inflammatory response triggered by P. falciparum in human peripheral blood mononuclear cells. Since the inflammatory reaction induced by P. falciparum is considered a major cause of malaria pathogenesis, identifying the mechanisms used by the parasite to induce the host inflammatory response is essential to develop urgently needed therapies against this disease.
Orengo
Jamie Marie
JM
Department of Medical Parasitology, NYU School of Medicine, New York, NY, USA.
Leliwa-Sytek
Aleksandra
A
Evans
James E
JE
Evans
Barbara
B
van de Hoef
Diana
D
Nyako
Marian
M
Day
Karen
K
Rodriguez
Ana
A
D000493:Allopurinol / Q000494:pharmacology; D000818:Animals; D004912:Erythrocytes / Q000469:parasitology; D006801:Humans; D007249:Inflammation / Q000209:etiology*; D018836:Inflammation Mediators / Q000378:metabolism; D010963:Plasmodium falciparum / Q000502:physiology*; D014527:Uric Acid / Q000037:antagonists & inhibitors / Q000378:metabolism*
D018836:Inflammation Mediators; D014527:Uric Acid; D000493:Allopurinol