Low-Dose Amphotericin B and Murine Dialyzable Spleen Extracts Protect against Systemic Candida Infection in Mice

Candida albicans causes opportunistic systemic infections with high mortality (30%–50%). Despite significant nephrotoxicity, amphotericin (AmB) is still used for the treatment of this serious fungal infection. Therefore, alternative treatments are urgently needed. Dialyzable leukocyte extracts have...

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Bibliographic Details
Published in:Clinical & developmental immunology 2013-01, Vol.2013 (2013), p.1-7
Main Authors: Estrada-Garcia, Iris, Estrada-Parra, Sergio, González-González, G., Wong-Baeza, Isabel, Hernández-Pando, Rogelio, Pavon, L., Limón-Flores, A., Perez-Tapia, S. M., Robledo-Ávila, F., Tovar, C.
Format: Article
Language:English
Subjects:
Amphotericin B
Amphotericin B - administration & dosage
Animals
Antifungal Agents - administration & dosage
Candida albicans
Candidiasis - drug therapy
Candidiasis - mortality
Candidiasis - pathology
Cytokines - biosynthesis
Disease Models, Animal
Female
Hepcidins - biosynthesis
Interleukin-6 - biosynthesis
Kidney - metabolism
Kidney - microbiology
Lymphokines - administration & dosage
Mice
Spleen - metabolism
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Summary:Candida albicans causes opportunistic systemic infections with high mortality (30%–50%). Despite significant nephrotoxicity, amphotericin (AmB) is still used for the treatment of this serious fungal infection. Therefore, alternative treatments are urgently needed. Dialyzable leukocyte extracts have been used successfully to treat patients with mucocutaneous candidiasis, but their effectiveness in systemic candidiasis has not been evaluated. In this study, low-dose AmB (0.1 mg/kg) plus 10 pg of murine dialyzable spleen extracts (mDSE) were tested in a systemic candidiasis mouse model. Survival, tissue fungal burden, kidney damage, kidney cytokines, and serum levels of IL-6 and hepcidin were evaluated. Our results showed that the combined treatment of low-dose AmB plus mDSE improved survival and reduced kidney fungal burden and histopathology; these effects correlated with increased kidney concentration of IFN-γ and TGF-β1, decreased levels of TNF-α, IL-6, and IL-10, as well as high levels of systemic IL-6 and hepcidin. Low-dose AmB and mDSE synergized to clear the infectious agent and reduced tissue damage, confirming the efficacy of a low dose of AmB, which might decrease the risk of drug toxicity. Further studies are necessary to explore these findings and its implications in future therapeutic approaches.
ISSN:2314-8861
1740-2522
2314-7156
1740-2530
DOI:10.1155/2013/194064