Effects of immunomodulatory drugs on plasma inflammatory markers in a rabbit model of atherosclerosis.
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.
Department of Biochemistry, Faculty of Pharmacy, University of Beni Sueif, Beni Sueif 62514, Egypt. mahahoussen@yahoo.com
Maha E
ME
Houssen
Mona M
MM
Haron
Sheren S
SS
Metwally
Tarek M
TM
Ibrahim
D000818:Animals; D050197:Atherosclerosis / Q000097:blood* / Q000188:drug therapy*; D000069059:Atorvastatin; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000187:drug effects / Q000378:metabolism; D002784:Cholesterol / Q000097:blood / Q000378:metabolism; D002791:Cholesterol, Dietary / Q000494:pharmacology; D008076:Cholesterol, HDL / Q000187:drug effects / Q000378:metabolism; D008078:Cholesterol, LDL / Q000097:blood / Q000187:drug effects; D016572:Cyclosporine / Q000494:pharmacology; D006538:Heptanoic Acids / Q000494:pharmacology; D007155:Immunologic Factors / Q000494:pharmacology*; D007249:Inflammation / Q000188:drug therapy*; D007371:Interferon-gamma / Q000097:blood / Q000187:drug effects; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D010949:Plasma / Q000187:drug effects; D011758:Pyrroles / Q000494:pharmacology; D011817:Rabbits; D016559:Tacrolimus / Q000494:pharmacology; D014280:Triglycerides / Q000097:blood
D015415:Biomarkers; D002791:Cholesterol, Dietary; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D006538:Heptanoic Acids; D007155:Immunologic Factors; D015850:Interleukin-6; D011758:Pyrroles; D014280:Triglycerides; D007371:Interferon-gamma; D016572:Cyclosporine; D002097:C-Reactive Protein; D002784:Cholesterol; D000069059:Atorvastatin; D016559:Tacrolimus