Effects of immunomodulatory drugs on plasma inflammatory markers in a rabbit model of atherosclerosis |
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Authors: | Maha E Houssen Mona M Haron Sheren S Metwally Tarek M Ibrahim |
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Institution: | (1) Department of Biochemistry, Faculty of Pharmacy, University of Beni Sueif, Beni Sueif, 62514, Egypt;(2) Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura, 35516, Egypt;(3) Department of Clinical Pathology, Faculty of Medicine, Mansoura University, Mansoura, 35516, Egypt |
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Abstract: | Atherosclerosis is a chronic disease of the arterial wall where both innate and adaptive immuno-inflammatory mechanisms are
involved. Inflammatory cytokines are implicated in the development and progression of atherosclerotic lesions. Immunomodulatory
therapies have been proposed for the treatment of atherosclerosis. Therefore, the aim of this study was to investigate the
systemic anti-inflammatory and immunomodulatory effects of atorvastatin, cyclosporine A (CsA), and tacrolimus (FK506) on plasma
inflammatory markers in atherosclerotic rabbits. Male New Zealand rabbits were randomized into five groups each of 12 animals.
Standard diet-fed group served as control, and the cholesterol-fed group received a diet supplemented with 1% cholesterol
alone, cholesterol + atorvastatin, cholesterol + FK506, and cholesterol + CsA. Serum levels of lipid profile parameters (triglycerides,
cholesterol, and high-density lipoprotein) were measured using colorimetric methods. Serum levels of C-reactive protein (CRP),
interleukin-6 (Il-6), and interferon-gamma (INF-γ) were measured in all studied groups using ELISA techniques. Our results
revealed a significant decrease (p < 0.001) in the serum levels of lipid profile parameters, CRP, Il-6, and INF-γ in atorvastatin-treated group compared with
the cholesterol-fed group. On the other hand, a non-significant difference was observed for the same parameters in either
FK506- or CsA-treated groups compared with the cholesterol-fed group. In conclusion, atorvastatin has a systemic anti-inflammatory
role that far surpassed the cholesterol reduction effect alone. FK506 or CsA failed to suppress elevated plasma inflammatory
markers. Thus, low doses of these two immunomodulating drugs could not have generalized systemic anti-inflammatory or immunosuppressive
effects. |
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