Simvastatin and fluvastatin reduce interleukin-6 and interleukin-8 lipopolysaccharide (LPS) stimulated production by isolated human monocytes from chronic kidney disease patients

Background: Statins reduce lipid levels, inflammation and cardiovascular events in patients with coronary artery disease; CKD patients show increased risk of cardiovascular and increased plasma levels of IL-6 and IL-8. Aim: To evaluate the in vitro effect of sirnvastatin (S) or fluvastatin (F) on the lipopolysaccharide (LPS) stimulated secretion of IL-6 and IL-8 from monocytes of chronic kidney disease patients (CKD) in K-DOQI stages 3-5. Methods and subjects: Monocytes enriched peripheral blood (PBMC) from 28 CKD (15 in K-DOQI stages 3-4, Group 1, and 13 in K-DOQI stage 5 on hemodialysis, Group 11) and 10 healthy subjects (HS), were isolated by Ficoll-gradient centrifugation. Cells were incubated with LPS 100 ng/ ml or with LPS plus increasing doses of statins (from 10(-6) to 10(-8) M) for 24 h. Surnatant IL-6 and IL-8 concentrations were determined by EIA. Results: Basally the mean concentration of EL-6 and IL-8 was higher in patients than in HS and in Group II than in Group I (EL6: HS 285 +/- 77 pg/ml, Group I 365 +/- 178 pg/ml, Group II 520 +/- 139 pg/ml- IL8 HS 180 +/- 75 pg/ml, Group I 1722 +/- 582 pg/ml, Group II 4400 +/- 1935 pg/ml). After addition of LPS the mean concentration of IL-6 and IL-8 increased in all groups (IL6: HS 1740 +/- 178 pg/ml, Group I 3754 +/- 672 pg/ml, Group 114800 967 pg/ml; IL8: HS 450 132 pg/ml, Group 1 9700 2837 pg/ml, Group 1111608 2316 pg/ml). After the addition of LPS plus increasing doses of S or F from 10(-10) to 10(-6) M, a significantly lower cytokine concentration compared to the data after LPS alone was observed (IL6: HS 45%, Group I 75%, Group II 50%; IL8: HS 100%, Group I 65%, Group II 35%). Conclusions: These data confirm that cytokine release is increased in CKD patients and that is highest in the most severe patients. Furthermore they suggest that fluvastatin or simvastatin can be used in order to reduce the high cardiovascular risk. (C) 2007 Elsevier Masson SAS. All rights reserved.