title: Effect of pentoxifylline on cytokine patterns in the therapy of complicated Plasmodium falciparum malaria.
abstract: 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.
authors.affiliation: Department of Infectious Diseases, Internal Medicine 1, University Hospital of Vienna, Austria.
authors.forename: C
authors.initials: C
authors.lastname: Wenisch
authors.forename: S
authors.initials: S
authors.lastname: Looareesuwan
authors.forename: P
authors.initials: P
authors.lastname: Wilairatana
authors.forename: B
authors.initials: B
authors.lastname: Parschalk
authors.forename: S
authors.initials: S
authors.lastname: Vannapann
authors.forename: V
authors.initials: V
authors.lastname: Wanaratana
authors.forename: W
authors.initials: W
authors.lastname: Wernsdorfer
authors.forename: W
authors.initials: W
authors.lastname: Graninger
mesh_terms: D000962:Antimalarials / Q000627:therapeutic use; D037621:Artemisinins; D000077332:Artesunate; D016207:Cytokines / Q000097:blood* / Q000187:drug effects; D004359:Drug Therapy, Combination; D005334:Fever; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D016778:Malaria, Falciparum / Q000150:complications / Q000188:drug therapy* / Q000276:immunology; D018512:Parasitemia / Q000188:drug therapy; D010431:Pentoxifylline / Q000494:pharmacology / Q000627:therapeutic use*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D019947:Receptors, Interleukin-6 / Q000097:blood / Q000187:drug effects; D018124:Receptors, Tumor Necrosis Factor / Q000097:blood / Q000187:drug effects; D012717:Sesquiterpenes / Q000627:therapeutic use; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000187:drug effects; D000093242:Interleukin-6 Inhibitors
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D000077332:Artesunate; D016207:Cytokines; D015850:Interleukin-6; D010431:Pentoxifylline; D010726:Phosphodiesterase Inhibitors; D019947:Receptors, Interleukin-6; D018124:Receptors, Tumor Necrosis Factor; D012717:Sesquiterpenes; D014409:Tumor Necrosis Factor-alpha; D000093242:Interleukin-6 Inhibitors