Effect of Simvastatin on Inflammatory Cytokines Balance in Air Pouch Granuloma Model
Hanan M. Hassan, Mohammed M.H. Al-Gayyar, Amal M. El-Gayar and Tarek M. Ibrahim
Affiliation: Department of Clinical Biochemistry, Faculty of Pharmacy, University of Mansoura, Mansoura 35516, Egypt.
Simvastatin has important immune-modulatory and anti-inflammatory effects independent of lipid lowering
effects. Therefore, our study was conducted to investigate the anti-inflammatory effects of simvastatin either alone or in
combination with aspirin. Air pouch granuloma model was used for induction of inflammation in 72 male Wistar albino
rats, which were treated with simvastatin (20 mg/kg/day), aspirin (25 mg/kg/day) or both for 3 or 6 executive days.
Inflammatory exudates were collected and measured. Oxidative stress was assessed by measuring exudates'
malondialdehyde (MDA) and nitric oxide (NO). Inflammatory mediator C-reactive protein (CRP) was investigated using
slide agglutination test. Exudates' levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-4 were measured by
ELISA. We found that simvastatin alone or in combination with aspirin exerts anti-inflammatory effects by reducing
volume of exudates. Simvastatin significantly reduced serum level of CRP and exudates levels of TNF-α, IL-6 and MDA
as well as significantly elevated exudates level of NO and IL-4. The results of simvastain were comparable to those of
aspirin. In conclusion, air pouch granuloma interrupted the balance between inflammatory and anti-inflammatory markers,
which is restored by simvastatin. The anti-inflammatory effects of simvastatin are comparable to aspirin and their
combination may produce better effects especially in the attenuation of the oxidative stress and IL-6.
Keywords: Air pouch granuloma, Aspirin, C-reactive protein (CRP), IL-4, IL-6, simvastatin, tumor necrosis factor (TNF)-α.
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