Effect of simvastatin or its combination with ezetimibe on Toll-like receptor expression and lipopolysaccharide – Induced cytokine production in monocytes of hypercholesterolemic patients

Abstract Objectives Toll-like receptors (TLRs) are key players in the innate immune system. Recently, a pivotal role of TLR2 and TLR4 has been recognized in atherogenesis. We investigated the effect of simvastatin monotherapy or its combination with ezetimibe on TLR2 and TLR4 membrane expression and on lipopolysaccharide (LPS)-induced interleukin-1β (IL-1β) and interleukin-6 (IL-6) production in peripheral blood monocytes of patients with primary hypercholesterolemia. Methods This was a prospective, randomized, open-label, blinded endpoint study. After a 3-month period of lifestyle changes patients ( n = 60) (mean age 55 ± 13) with LDL-cholesterol levels above those recommended by the NCEP ATP III, were randomly allocated to open-label simvastatin 40 mg ( n = 30) or simvastatin/ezetimibe 10/10 mg ( n = 30) daily. Both groups were similar with regard to demographics, risk factors, medications and baseline lipid values. TLR2 and TLR4 membrane expression in monocytes, LPS-induced intracellular production of IL-1β and IL-6 were assessed by flow cytometry at baseline and 3 months post-treatment in both patient groups, as well as in 30 age- and sex-matched normolipidemic controls. Results Hypercholesterolemic patients exhibited higher TLR2 and TLR4 membrane expression compared with controls ( p