PMID- 20835848 OWN - NLM STAT- MEDLINE DCOM- 20110519 LR - 20211020 IS - 1573-0832 (Electronic) IS - 0301-486X (Linking) VI - 171 IP - 3 DP - 2011 Mar TI - Cyclosporin A treatment and decreased fungal load/antigenemia in experimental murine paracoccidioidomycosis. PG - 161-9 LID - 10.1007/s11046-010-9359-5 [doi] AB - 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. FAU - Massuda, T Y C AU - Massuda TY AD - Department of Pathology Sciences, State University of Londrina, CCB, Universidade Estadual de Londrina, Campus Universitario, Londrina, PR 86051-970, Brazil. FAU - Nagashima, L A AU - Nagashima LA FAU - Leonello, P C AU - Leonello PC FAU - Kaminami, M S AU - Kaminami MS FAU - Mantovani, M S AU - Mantovani MS FAU - Sano, A AU - Sano A FAU - Uno, J AU - Uno J FAU - Venancio, E J AU - Venancio EJ FAU - Camargo, Z P AU - Camargo ZP FAU - Itano, E N AU - Itano EN LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20100911 PL - Netherlands TA - Mycopathologia JT - Mycopathologia JID - 7505689 RN - 0 (43 kDa protein, Paracoccidioides) RN - 0 (Antibodies, Fungal) RN - 0 (Antigens, Fungal) RN - 0 (Fungal Proteins) RN - 0 (Glycoproteins) RN - 0 (Immunoglobulin G) RN - 0 (Tumor Necrosis Factor-alpha) RN - 130068-27-8 (Interleukin-10) RN - 207137-56-2 (Interleukin-4) RN - 82115-62-6 (Interferon-gamma) RN - 83HN0GTJ6D (Cyclosporine) SB - IM MH - Animals MH - Antibodies, Fungal/blood MH - Antigens, Fungal/blood/immunology MH - Colony Count, Microbial MH - Cyclosporine/immunology/*therapeutic use MH - Enzyme-Linked Immunosorbent Assay MH - Fungal Proteins/blood/immunology MH - Glycoproteins/blood/immunology MH - Hypersensitivity, Delayed/immunology MH - Immunoglobulin G/blood MH - Interferon-gamma/blood MH - Interleukin-10/blood MH - Interleukin-4/blood MH - Liver/microbiology/pathology MH - Lung/*microbiology/pathology MH - Lymphocyte Activation MH - Lymphocytes/immunology MH - Male MH - Mice MH - Mice, Inbred BALB C MH - *Paracoccidioides/drug effects/growth & development/immunology MH - Paracoccidioidomycosis/*drug therapy/immunology/microbiology/pathology MH - Tumor Necrosis Factor-alpha/blood EDAT- 2010/09/14 06:00 MHDA- 2011/05/20 06:00 CRDT- 2010/09/14 06:00 PHST- 2010/06/01 00:00 [received] PHST- 2010/08/25 00:00 [accepted] PHST- 2010/09/14 06:00 [entrez] PHST- 2010/09/14 06:00 [pubmed] PHST- 2011/05/20 06:00 [medline] AID - 10.1007/s11046-010-9359-5 [doi] PST - ppublish SO - Mycopathologia. 2011 Mar;171(3):161-9. doi: 10.1007/s11046-010-9359-5. Epub 2010 Sep 11.