RRC ID 46922
Author Massuda TY, Nagashima LA, Leonello PC, Kaminami MS, Mantovani MS, Sano A, Uno J, Venancio EJ, Camargo ZP, Itano EN.
Title Cyclosporin A treatment and decreased fungal load/antigenemia in experimental murine paracoccidioidomycosis.
Journal Mycopathologia
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 10⁵ 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-γ, TNF-α, 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-γ, TNF-α 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.
Volume 171(3)
Pages 161-9
Published 2011-3-1
DOI 10.1007/s11046-010-9359-5
PMID 20835848
MeSH Animals Antibodies, Fungal / blood Antigens, Fungal / blood Antigens, Fungal / immunology Colony Count, Microbial Cyclosporine / immunology Cyclosporine / therapeutic use* Enzyme-Linked Immunosorbent Assay Fungal Proteins / blood Fungal Proteins / immunology Glycoproteins / blood Glycoproteins / immunology Hypersensitivity, Delayed / immunology Immunoglobulin G / blood Interferon-gamma / blood Interleukin-10 / blood Interleukin-4 / blood Liver / microbiology Liver / pathology Lung / microbiology* Lung / pathology Lymphocyte Activation Lymphocytes / immunology Male Mice Mice, Inbred BALB C Paracoccidioides* / drug effects Paracoccidioides* / growth & development Paracoccidioides* / immunology Paracoccidioidomycosis / drug therapy* Paracoccidioidomycosis / immunology Paracoccidioidomycosis / microbiology Paracoccidioidomycosis / pathology Tumor Necrosis Factor-alpha / blood
IF 2.452
Times Cited 5
Pathogenic microorganisms