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Title: Cyclosporin A Treatment and Decreased Fungal Load/Antigenemia in Experimental Murine Paracoccidioidomycosis
Authors: Massuda, T. Y. C.
Nagashima, L. A.
Leonello, P. C.
Kaminami, M. S.
Mantovani, M. S.
Sano, A.
Uno, J.
Venancio, E. J.
Camargo, Z. P. [UNIFESP]
Itano, E. N.
Universidade Estadual de Londrina (UEL)
Chiba Univ
Universidade Federal de São Paulo (UNIFESP)
Keywords: Immunosuppression
Paracoccidioides brasiliensis
Antifungal drug
Lymphoproliferative response
Issue Date: 1-Mar-2011
Publisher: Springer
Citation: Mycopathologia. Dordrecht: Springer, v. 171, n. 3, p. 161-169, 2011.
Abstract: Paracoccidioidomycosis (PCM) is a systemic mycosis caused by the fungus Paracoccidioides brasiliensis (Pb). the cyclosporin A (CsA) is an immunosuppressant drug that inhibits calcineurin and has been described as a potential antifungal drug. the present study investigated the effect of CsA on the immune response, fungal load/antigenemia in experimental murine PCM. It was used four groups of BALB/c mice: (a) infected with 1 x 10(5) Pb18 yeast cells (Pb), (b) infected and treated with CsA every other day 10 mg/kg of CsA (s.c.) during 30 days (Pb/CsA), (c) treated with CsA (CsA) and (d) no infected/treated (PBS). the immune response was evaluated by lymphocyte proliferation, DTH assays to exoAgs, ELISA for IgG anti-gp43 (specific immune responses) and cytokine serum levels (IFN-gamma, TNF-alpha, IL-4 and IL-10). Fungal load was determined by lung colony-forming units (CFU) counts, lung and liver histopathology analysis and antigenemia determined by inhibition-ELISA. As expected, CsA was able to inhibit the specific cellular and humoral immune response (P < 0.05), with decrease in serum IFN-gamma, TNF-alpha and IL-4 levels (P < 0.05). Cyclosporin A treatment also resulted in significantly decreased lung Pb CFU (P < 0.05) as well as a lower number of yeasts in the lung and liver (P < 0.05) by histopathology. in concordance, the decreased antigenemia was observed in Pb/CsA group (P < 0.05). in conclusion, even with immunosuppressive action, treatment with CsA results in decreased lung fungal load/antigenemia in experimental PCM in BALB/c mice. Further study is required to determine whether this represents less severe disease or protection by CsA.
ISSN: 0301-486X
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