title: Cyclosporin A treatment and decreased fungal load/antigenemia in experimental murine paracoccidioidomycosis.
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.
authors.affiliation: Department of Pathology Sciences, State University of Londrina, CCB, Universidade Estadual de Londrina, Campus Universitário, Londrina, PR 86051-970, Brazil.
authors.forename: T Y C
authors.initials: TY
authors.lastname: Massuda
authors.forename: L A
authors.initials: LA
authors.lastname: Nagashima
authors.forename: P C
authors.initials: PC
authors.lastname: Leonello
authors.forename: M S
authors.initials: MS
authors.lastname: Kaminami
authors.forename: M S
authors.initials: MS
authors.lastname: Mantovani
authors.forename: A
authors.initials: A
authors.lastname: Sano
authors.forename: J
authors.initials: J
authors.lastname: Uno
authors.forename: E J
authors.initials: EJ
authors.lastname: Venancio
authors.forename: Z P
authors.initials: ZP
authors.lastname: Camargo
authors.forename: E N
authors.initials: EN
authors.lastname: Itano
mesh_terms: D000818:Animals; D000908:Antibodies, Fungal / Q000097:blood; D000946:Antigens, Fungal / Q000097:blood / Q000276:immunology; D015169:Colony Count, Microbial; D016572:Cyclosporine / Q000276:immunology / Q000627:therapeutic use*; D004797:Enzyme-Linked Immunosorbent Assay; D005656:Fungal Proteins / Q000097:blood / Q000276:immunology; D006023:Glycoproteins / Q000097:blood / Q000276:immunology; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood; D007371:Interferon-gamma / Q000097:blood; D016753:Interleukin-10 / Q000097:blood; D015847:Interleukin-4 / Q000097:blood; D008099:Liver / Q000382:microbiology / Q000473:pathology; D008168:Lung / Q000382:microbiology* / Q000473:pathology; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010228:Paracoccidioides / Q000187:drug effects / Q000254:growth & development / Q000276:immunology; D010229:Paracoccidioidomycosis / Q000188:drug therapy* / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: C103180:43 kDa protein, Paracoccidioides; D000908:Antibodies, Fungal; D000946:Antigens, Fungal; D005656:Fungal Proteins; D006023:Glycoproteins; D007074:Immunoglobulin G; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma; D016572:Cyclosporine