Department of Pathology Sciences, State University of Londrina, CCB, Universidade Estadual de Londrina, Campus Universitário, Londrina, PR 86051-970, Brazil.
Mycopathologia. 2011 Mar;171(3):161-9. doi: 10.1007/s11046-010-9359-5. Epub 2010 Sep 11.
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.
球孢子菌病（PCM）是一种由巴西副球孢子菌（Pb）引起的系统性真菌病。环孢素 A（CsA）是一种免疫抑制剂，它抑制钙调神经磷酸酶，被描述为一种有潜力的抗真菌药物。本研究调查了 CsA 对实验性 PCM 中免疫反应、真菌负荷/抗原血症的影响。使用了四组 BALB/c 小鼠：（a）感染 1 x 10⁵ Pb18 酵母细胞（Pb），（b）感染并每隔一天用 CsA 治疗 10mg/kg CsA（sc），共 30 天（Pb/CsA），（c）用 CsA 治疗（CsA），（d）未感染/未治疗（PBS）。通过淋巴细胞增殖、外 Ag 的 DTH 测定、IgG 抗 gp43 的 ELISA（特异性免疫反应）和细胞因子血清水平（IFN-γ、TNF-α、IL-4 和 IL-10）评估免疫反应。通过肺集落形成单位（CFU）计数、肺和肝组织病理学分析以及抑制 ELISA 测定抗原血症来确定真菌负荷。如预期的那样，CsA 能够抑制特异性细胞和体液免疫反应（P < 0.05），导致血清 IFN-γ、TNF-α 和 IL-4 水平降低（P < 0.05）。CsA 治疗还导致肺 Pb CFU 显著减少（P < 0.05），以及肺和肝组织病理学中酵母数量减少（P < 0.05）。相应地，在 Pb/CsA 组观察到抗原血症减少（P < 0.05）。总之，即使具有免疫抑制作用，CsA 治疗也会导致 BALB/c 小鼠实验性 PCM 中肺真菌负荷/抗原血症减少。需要进一步研究以确定这是否代表疾病较轻或 CsA 保护。
