The effect of atorvastatin and its role on systemic cytokine network in treatment of acute experimental colitis

• Published in: Immunopharmacology and immunotoxicology 2011-12, Vol.33 (4), p.667-675
• Main Authors: Aktunc, Erol, Kayhan, Basak, Arasli, Mehmet, Gun, Banu Dogan, Barut, Figen
• Format: Article
• Language: English
• Subjects: Acute Disease; Animals; Atorvastatin Calcium; Colitis - blood; Colitis - chemically induced; Colitis - drug therapy; Colitis - immunology; cytokines; Cytokines - blood; Cytokines - immunology; Disease Models, Animal; Down-Regulation - drug effects; Down-Regulation - immunology; Heptanoic Acids - pharmacology; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors - pharmacology; Immunologic Factors - pharmacology; Inflammatory bowel diseases; Mice; Mice, Inbred BALB C; Pyrroles - pharmacology; statin; systemic immune response; Th1; Th1 Cells - immunology; Th17; Th2; Th2 Cells - immunology
• ISSN: 0892-3973; 1532-2513
• DOI: 10.3109/08923973.2011.559475

Inflammatory bowel diseases are characterized by disabilities in gastrointestinal system and defects in mucosal immune system. Statins are 3-hydroxy-3-methyl glutaryl coenzyme A reductase inhibitor and are used to treat hypercholesterolemia in patients with coronary artery and atherosclerotic diseases. Recent studies have demonstrated that statins have immunomodulatory role by effecting different pathways in immune system. In this study, we investigated the effect of atorvastatin and its mechanism on systemic immune response in treatment of trinitrobenzene sulfonic acid (TNBS)-induced colitis mice. We observed that atorvastatin significantly suppressed the severity of TNBS-induced colitis in BALB/c mice. This was manifested in reduced rectal bleeding, decrease in colon length, reduction of histological damage, and improved survival. Concurrently, we investigated the immunomodulatory role of atorvastatin on systemic immune system. We investigated the proinflammatory (IL-1α, IL-6, TNF-α), Th1 (IFN-γ, IL-2), Th2 (IL-4, IL-5, IL-10), and Th17 (IL-17, IL-23) cytokine levels in serum samples of colitis and atorvastatin-administered mice. We discovered that administration of atorvastatin significantly down-regulates systemic TNF-α level and Th17 cytokine levels. Furthermore, atorvastatin treatment switches Th1 type T-cell response toward/to Th2 (IL-4, IL-10) type response.