Kostadinov Ilia, Delev Delian, Petrova Atanaska, Stanimirova Irina, Draganova Krassimira, Kostadinova Ivanka, Murdjeva Marianna
Department of Pharmacology and Clinical Pharmacology, Medical Faculty, Medical University-Plovdiv , Plovdiv , Bulgaria.
Department of Microbiology and Immunology, Faculty of Pharmacy, Medical University-Plovdiv , Plovdiv , Bulgaria.
Biotechnol Biotechnol Equip. 2014 May 4;28(3):552-558. doi: 10.1080/13102818.2014.932136. Epub 2014 Sep 25.
The aim of the present study was to evaluate the anti-inflammatory effect of clomipramine in carrageenan- and lipopolysaccharide-induced (LPS-induced) models of inflammation by investigating the changes in serum levels of the pro-inflammatory cytokine TNF-α and the anti-inflammatory cytokines IL-10 and TGF-β after single and repeated administration of the drug. In order to study the effect of single and repeated doses of clomipramine on carrageenan-induced paw oedema, male Wistar rats were divided in five groups ( = 8): control, positive control group and three experimental groups treated with 5, 10 and 20 mg/kg bw clomipramine, respectively. The effect of single and repeated doses of clomipramine on serum cytokine levels was studied as animals were divided in four groups: two control groups treated with saline and two experimental groups treated with clomipramine 20 mg/kg bw. Carrageenan and LPS were injected immediately after clomipramine or saline injection. Serum cytokine concentrations were tested by enzyme immunoassay. Following acute administration only the highest dose that was used inhibited the carrageenan-induced inflammation. Oedema inhibition was observed with 5, 10 and 20 mg/kg bw clomipramine after repeated administration. Single and repeated administration of clomipramine at a dose of 20 mg/kg bw did not significantly change the serum levels of TGF-1β, IL-10 and TNF-α when compared to the controls in carrageenan-induced inflammation. Following LPS-induced inflammation clomipramine significantly increased the serum levels of TGF-1β after repeated administration and decreased TNF-α in rats after single-dose and repeated pretreatment with 20 mg/kg bw clomipramine. A significant increase in the levels of IL-10 in relation to this inflammatory model was observed only in single dose treated animals. Clomipramine possesses an anti-inflammatory effect in the carrageenan-induced model of exudative inflammation. In LPS-induced inflammation, clomipramine showed an immunomodulatory effect, decreasing TNF-α and increasing TGF-1β after repeated administration, and increasing IL-10 after a single dose.
本研究的目的是通过研究单次和重复给药后促炎细胞因子TNF-α以及抗炎细胞因子IL-10和TGF-β血清水平的变化，评估氯米帕明在角叉菜胶和脂多糖诱导（LPS诱导）的炎症模型中的抗炎作用。为了研究单次和重复剂量的氯米帕明对角叉菜胶诱导的爪肿胀的影响，将雄性Wistar大鼠分为五组（每组n = 8）：对照组、阳性对照组和三个分别用5、10和20 mg/kg体重氯米帕明处理的实验组。由于将动物分为四组来研究单次和重复剂量的氯米帕明对血清细胞因子水平的影响：两个用生理盐水处理的对照组和两个用20 mg/kg体重氯米帕明处理的实验组。在注射氯米帕明或生理盐水后立即注射角叉菜胶和LPS。通过酶免疫测定法检测血清细胞因子浓度。急性给药后，仅所使用的最高剂量抑制了角叉菜胶诱导的炎症。重复给药后，5、10和20 mg/kg体重的氯米帕明均观察到水肿抑制作用。与角叉菜胶诱导的炎症中的对照组相比，以20 mg/kg体重单次和重复给药氯米帕明并未显著改变TGF-1β、IL-10和TNF-α的血清水平。在LPS诱导的炎症后，重复给药后氯米帕明显著增加了TGF-1β的血清水平，并且在以20 mg/kg体重单次给药和重复预处理后降低了大鼠体内的TNF-α。仅在单次给药处理的动物中观察到与该炎症模型相关的IL-10水平显著升高。氯米帕明在角叉菜胶诱导的渗出性炎症模型中具有抗炎作用。在LPS诱导的炎症中，氯米帕明显示出免疫调节作用，重复给药后降低TNF-α并增加TGF-1β，单次给药后增加IL-10。
