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Journal of Antimicrobial Chemotherapy (1996) 37, 943-954
© 1996 The British Society for Antimicrobial Chemotherapy

research-article

Effect of pentoxifylline on the course of systemic Candida albicans infection in mice

A. Louiea,c,*, A. L. Baltcha,c, M. A. Frankea, W. J. Ritza, R. P. Smitha,c, J. K. Singhb,d and M. A. Gordone

aInfectious Disease Section, Medical Service Albany, New York 12208, USA bPathology Section, Laboratory Service, Stratton Veterans Affairs Medical Center Albany, New York 12208, USA cDivision of Infections Diseases, Department of Medicine Albany, New York 12208, USA dDepartment of Pathology, Albany Medical College Albany, New York 12208, USA eMycology Laboratory of the Wadsworth Center for Laboratories and Research, New York State Department of Health Albany, New York 12201, USA

Received 12 April 1995; accepted 10 November 1995

*Corresponding author: Dr Arnold Louie, Division of Infectious Diseases, A-49, Albany Medical College, 47 New Scotland Avenue, Albany, New York 12208, USA

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 100mg/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.


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K. Miller, A. Louie, A. L. Baltch, R. P. Smith, P. J. Davis, and M. A. Gordon
Pharmacokinetics of Pentoxifylline and Its Metabolites in Healthy Mice and in Mice Infected with Candida albicans
Antimicrob. Agents Chemother., September 1, 1998; 42(9): 2405 - 2409.
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