title: Study on anti-inflammatory and immunomodulatory effects of clomipramine in carrageenan- and lipopolysaccharide-induced rat models of inflammation.
abstract: 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 (n= 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.
authors.affiliation: Department of Pharmacology and Clinical Pharmacology, Medical Faculty, Medical University-Plovdiv , Plovdiv , Bulgaria.
authors.forename: Ilia
authors.initials: I
authors.lastname: Kostadinov
authors.affiliation: Department of Pharmacology and Clinical Pharmacology, Medical Faculty, Medical University-Plovdiv , Plovdiv , Bulgaria.
authors.forename: Delian
authors.initials: D
authors.lastname: Delev
authors.affiliation: Department of Microbiology and Immunology, Faculty of Pharmacy, Medical University-Plovdiv , Plovdiv , Bulgaria.
authors.forename: Atanaska
authors.initials: A
authors.lastname: Petrova
authors.affiliation: Department of Microbiology and Immunology, Faculty of Pharmacy, Medical University-Plovdiv , Plovdiv , Bulgaria.
authors.forename: Irina
authors.initials: I
authors.lastname: Stanimirova
authors.affiliation: Department of Microbiology and Immunology, Faculty of Pharmacy, Medical University-Plovdiv , Plovdiv , Bulgaria.
authors.forename: Krassimira
authors.initials: K
authors.lastname: Draganova
authors.affiliation: Department of Pharmacology and Clinical Pharmacology, Medical Faculty, Medical University-Plovdiv , Plovdiv , Bulgaria.
authors.forename: Ivanka
authors.initials: I
authors.lastname: Kostadinova
authors.affiliation: Department of Microbiology and Immunology, Faculty of Pharmacy, Medical University-Plovdiv , Plovdiv , Bulgaria.
authors.forename: Marianna
authors.initials: M
authors.lastname: Murdjeva
keywords: carrageenan; clomipramine; cytokines; inflammation; lipopolysaccharide