Enhancement by ubenimex (bestatin) of host resistance to Candida albicans infection.
Ubenimex is a low molecular weight microbial metabolite which has been demonstrated to have antitumor and immunomodulatory activities. In this study, the protective effect of ubenimex on Candida albicans infection was investigated in normal and immunosuppressed mice. In normal mice, treatment with ubenimex at 0.5, 5 and 25 mg/kg for 5 days prior to infection prolonged survival time in a dose-dependent manner. In immunosuppressed mice treated with a single dose of cyclophosphamide 4 days prior to infection, ubenimex treatment at 5 mg/kg for 5 days significantly increased the number of survivors. Ubenimex-treated mice had a significant increase in number of peritoneal exudate cells with neutrophils as well as enhanced functions, including phagocytosis and active oxygen production. These results suggest the potential usefulness of ubenimex as a prophylactic agent for the management of patients with opportunistic fungal infections.
Aoyagi
K
K
Research Laboratory, Nippon Kayaku Co., Ltd., Tokyo, Japan.
Itoh
N
N
Abe
F
F
Abe
S
S
Uchida
K
K
Ishizuka
M
M
Takeuchi
T
T
Yamaguchi
H
H
D000818:Animals; D002177:Candidiasis / Q000276:immunology* / Q000517:prevention & control; D003520:Cyclophosphamide / Q000494:pharmacology; D005260:Female; D007113:Immunity, Innate / Q000187:drug effects; D007155:Immunologic Factors / Q000494:pharmacology* / Q000627:therapeutic use; D007165:Immunosuppression Therapy; D007930:Leucine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D008163:Luminescent Measurements; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology; D010587:Phagocytosis / Q000187:drug effects
D007155:Immunologic Factors; D003520:Cyclophosphamide; D007930:Leucine; C012211:ubenimex