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.


OBJECTIVE
To evaluate the in vitro effect of simvastatin (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
Monocytes enriched peripheral blood (PBMC) from 28 CKD (15 in K-DOQI stages 3-4, Group I, and 13 in K-DOQI stage 5 on hemodialysis, Group II) 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 IL-6 and IL-8 was higher in patients than in HS and in Group II than in Group I (IL6: 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 II 4800 +/- 967 pg/ml; IL8: HS 450+/-132 pg/ml, Group I 9700+/-2837 pg/ml, Group II 11608 +/- 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.
Mantuano
Emanuela
E
Department of Internal Medicine, Nephrology Section, University of Pisa, Italy.
Santi
Samuele
S
Filippi
Cristina
C
Manca-Rizza
Giovanni
G
Paoletti
Sabrina
S
Consani
Cristina
C
Giovannini
Luca
L
Tramonti
Gianfranco
G
Carpi
Angelo
A
Panichi
Vincenzo
V
D002318:Cardiovascular Diseases / Q000517:prevention & control; D002478:Cells, Cultured; D002908:Chronic Disease; D016207:Cytokines / Q000032:analysis; D005229:Fatty Acids, Monounsaturated / Q000494:pharmacology; D000077340:Fluvastatin; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D015850:Interleukin-6 / Q000096:biosynthesis*; D016209:Interleukin-8 / Q000096:biosynthesis*; D007674:Kidney Diseases / Q000188:drug therapy* / Q000473:pathology; D008070:Lipopolysaccharides / Q000494:pharmacology; D009000:Monocytes; D019821:Simvastatin / Q000494:pharmacology*
D016207:Cytokines; D005229:Fatty Acids, Monounsaturated; D007211:Indoles; D015850:Interleukin-6; D016209:Interleukin-8; D008070:Lipopolysaccharides; D000077340:Fluvastatin; D019821:Simvastatin