Effect of pentoxifylline on the course of systemic Candida albicans infection in mice.
Pentoxifylline can decrease the production of tumour necrosis factor alpha (TNF alpha) by endotoxin-stimulated macrophages and may improve survival in animals with overwhelming bacterial sepsis. In this study various doses of pentoxifylline were administered to mice with systemic Candida albicans infection to determine its effect on serum TNF alpha levels, organ fungal burden, and host survival. Intraperitoneal injections of pentoxifylline at 20 mg/kg every 8 h did not affect these endpoints. However, fungal counts were significantly higher in kidneys of animals that received 30 and 60 mg/kg of pentoxifylline every 8 h when compared to controls. Injection of 60 mg/kg of pentoxifylline at 8 h intervals also significantly shortened mean survival from 5.8 to 3.8 days (P = 0.01). Pentoxifylline did not affect peripheral WBC counts, serum TNF alpha and interleukin-6 levels, or the density of neutrophils in tissues. In vitro, pentoxifylline decreased the production of TNF alpha by C. albicans-stimulated macrophages in a dose-dependent manner, but only at concentrations greater than 100 mg/L. In contrast, pentoxifylline suppressed TNF alpha production by endotoxin-stimulated macrophages at concentrations as low as 10 mg/L. Thus, higher doses of pentoxifylline are detrimental in systemic C. albicans infection. However, the detrimental effect is not mediated by alterations in serum TNF alpha or interleukin-6 levels or the aggregation of neutrophils in tissues.
Louie
A
A
Infectious Disease Section, Stratton Veterans Affairs Medical Center, Albany, New York 12208, USA.
Baltch
A L
AL
Franke
M A
MA
Ritz
W J
WJ
Smith
R P
RP
Singh
J K
JK
Gordon
M A
MA
D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology*; D002177:Candidiasis / Q000188:drug therapy* / Q000401:mortality; D004731:Endotoxins / Q000633:toxicity; D006801:Humans; D015850:Interleukin-6 / Q000032:analysis; D007668:Kidney / Q000187:drug effects / Q000382:microbiology / Q000473:pathology; D007958:Leukocyte Count / Q000187:drug effects; D051379:Mice; D010431:Pentoxifylline / Q000494:pharmacology*; D015996:Survival Rate; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000187:drug effects
D000935:Antifungal Agents; D004731:Endotoxins; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; C044101:endotoxin, Escherichia coli; D010431:Pentoxifylline