Effect of pentoxifylline on cytokine patterns in the therapy of complicated Plasmodium falciparum malaria.

C WenischDepartment of Infectious Diseases, Internal Medicine 1, University Hospital of Vienna, Austria.

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S LooareesuwanDepartment of Infectious Diseases, Internal Medicine 1, University Hospital of Vienna, Austria.

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P WilairatanaDepartment of Infectious Diseases, Internal Medicine 1, University Hospital of Vienna, Austria.

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B ParschalkDepartment of Infectious Diseases, Internal Medicine 1, University Hospital of Vienna, Austria.

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S VannapannDepartment of Infectious Diseases, Internal Medicine 1, University Hospital of Vienna, Austria.

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V WanaratanaDepartment of Infectious Diseases, Internal Medicine 1, University Hospital of Vienna, Austria.

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W WernsdorferDepartment of Infectious Diseases, Internal Medicine 1, University Hospital of Vienna, Austria.

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W GraningerDepartment of Infectious Diseases, Internal Medicine 1, University Hospital of Vienna, Austria.

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The effect of pentoxifylline (PTX) was tested for its capacity to modulate cytokine responses during therapy of severe Plasmodium falciparum malaria in a placebo-controlled, randomized study in 45 adult patients in Bangkok, Thailand. The patients received standard antimalarial treatment with artesunate (120 mg intravenously given immediately, then 60 mg every 12 hr for a total dose of 600 mg). The patients received either low-dose PTX (20 mg/kg/day, n = 15), high-dose PTX (40 mg/kg/day, n = 15), or placebo (n = 15) as continuous infusion for the first three days of antimalarial treatment. Tumor necrosis factor (TNF) and interleukin-6 (IL-6) plasma levels were markedly elevated in all patients prior to treatment. After 6 hr of high-dose PTX treatment, TNF and IL-6 levels significantly decreased while an increase in TNF and IL-6 levels was seen after 6 hr of low-dose PTX or placebo treatment (P < 0.01). After 12 and 24 hr of high-dose PTX infusion, TNF-receptor plasma concentrations were lower than in low-dose PTX- or placebo-treated patients (P < 0.01), whereas no differences between the groups with regard to IL-6 receptor levels were observed. We conclude that 40 mg/kg/day of PTX reduces plasma levels of TNF, IL-6, and TNF-receptor in patients with severe malaria. Whether this reduction improves clinical outcome remains to be determined.

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