Monguilhott Dalmarco Eduardo, Fröde Tânia Silvia, Medeiros Yara Santos
Department of Clinical Analysis, Center of Health Sciences, Universidade Federal de Santa Catarina, Campus Universitário - Trindade, 88040-970 Florianopolis, SC, Brazil.
Transpl Immunol. 2004 Jan;12(2):151-7. doi: 10.1016/j.trim.2003.09.001.
It is well known that cyclosporin A (CsA) exhibits important anti-inflammatory effects, besides its immunosuppressive activity. However, the mechanisms by which CsA exerts these effects remain unclear.
This study evaluated whether the acute administration of CsA significantly interfered in leukocyte migration, exudation, myeloperoxidase (MPO) and adenosine-deaminase activities and nitrate/nitrite levels, in a mouse model of pleurisy.
Pleurisy was induced by carrageenan (1%) treatment and the parameters were analyzed 4 and 48 h after. Groups of animals were previously treated with different doses of CsA and compared with non-treated groups.
CsA (0.1-5 mg/kg, intraperitoneal, 1 h before pleurisy induction) inhibited neutrophil migration (P<0.05), but not the exudation that occurred 4 h after pleurisy induction. At this time, CsA (1 mg/kg, 1 h before) also decreased nitrate/nitrite levels and MPO activity (P<0.01). CsA (2 mg/kg, 0.5 h before) was also effective in decreasing mononuclear influx, exudation and nitrate/nitrite levels 48 h after onset of inflammation.
These results indicate that the acute administration of CsA is able to reduce the two leukocyte populations that occur both at 4 and 48 h after pleurisy induction, late exudation (48 h), MPO activity (4 h) and nitrate/nitrite levels (4 and 48 h). Taken together, these findings indicate that CsA has acute anti-inflammatory effects in immunocompetent animals.
众所周知,环孢素A(CsA)除了具有免疫抑制活性外,还具有重要的抗炎作用。然而,CsA发挥这些作用的机制仍不清楚。
本研究评估了在小鼠胸膜炎模型中,急性给予CsA是否会显著干扰白细胞迁移、渗出、髓过氧化物酶(MPO)和腺苷脱氨酶活性以及硝酸盐/亚硝酸盐水平。
通过角叉菜胶(1%)处理诱导胸膜炎,并在4小时和48小时后分析各项参数。预先用不同剂量的CsA对动物组进行处理,并与未处理组进行比较。
CsA(0.1 - 5毫克/千克,腹腔注射,在诱导胸膜炎前1小时)抑制中性粒细胞迁移(P<0.05),但不抑制胸膜炎诱导后4小时发生的渗出。此时,CsA(1毫克/千克,在诱导前1小时)也降低了硝酸盐/亚硝酸盐水平和MPO活性(P<0.01)。CsA(2毫克/千克,在诱导前0.5小时)在炎症发作48小时后也能有效减少单核细胞流入、渗出以及硝酸盐/亚硝酸盐水平。
这些结果表明,急性给予CsA能够减少胸膜炎诱导后4小时和48小时出现的两种白细胞群体、晚期渗出(48小时)、MPO活性(4小时)以及硝酸盐/亚硝酸盐水平(4小时和48小时)。综上所述,这些发现表明CsA在免疫活性动物中具有急性抗炎作用。