Anti-TNF effect of combined pravastatin and cilostazol treatment in an in vivo mouse model. (4th March 2019)

• Record Type: Journal Article
• Authors: Lee, Hae-Ri; Jo, Min-Kyung; Park, Kyung-Yeon; Jang, You-Jin; Heo, Tae-Hwe
• Is Part Of: Immunopharmacology and immunotoxicology. Volume 41:Number 2(2019)
• Page Start: 179
• Page End: 184
• Publication Date: 2019-03-04
• Subjects: Pravastatin -- cilostazol -- combination therapy -- inflammation -- TNF -- mice; Immunopharmacology -- Periodicals; Immunotoxicology -- Periodicals; Antibody-toxin conjugates -- Periodicals; Immunology -- Periodicals; 615.37
• DOI: 10.1080/08923973.2019.1569045
• Languages: English
• ISSNs: 0892-3973

Abstract

Abstract: Objectives: Pravastatin and cilostazol are used as lipid-lowering and antiplatelet agents, respectively. Regarding their well-known anti-inflammatory effects, the additive effect of the two drugs on anti-TNF functions has not yet been investigated. In the present investigation, the beneficial effect of combined pravastatin and cilostazol on their anti-TNF activities was assessed using an in vivo mouse model. Methods: Mice were pretreated with pravastatin and/or cilostazol (40 mg/kg of each), orally once two hour prior to an LPS (5 mg/kg, i.p.) challenge. One hour post challenge, blood and descending aorta were collected for serum TNF levels and immune cell infiltration analyses. For survival analysis, pravastatin and/or cilostazol (40 mg/kg of each) were administered 30 minutes prior tod -galactosamine administration (700 mg/kg, i.p.) and TNF (10 µg/kg, i.p.) challenge and mice survival was monitored. We also examined the effect of either drug or the combination of drugs on TNF-mediated MAPK and NF-κB signaling, using Western blot analysis. Results: Combined treatment of pravastatin and cilostazol significantly decreased serum TNF release and immune cell infiltration in the descending aorta following LPS administration, compared to each single treatment. Additionally, the combined drugs significantly decreased TNF-mediated mouse mortality and downregulated TNF-induced MAPK and NF-κB activation. Conclusions: These findings suggest that combined pravastatin and cilostazol is more effective for reducing TNF-driven inflammation through their anti-TNF activity than monotherapy.