Hypolipidemic drugs affect monocyte IL-1beta gene expression and release in patients with IIa and IIb dyslipidemia.

Because atherosclerosis has been provern to be an inflammatory disease, it became obvious that the proper treatment of dyslipidemic patients should not only correct lipid parameters but also inhibit the inflammatory state. One of the crucial proinflammatory and procoagulant cytokines participating in the pathogenesis of atherosclerosis is interleukin-1β (IL-1β). Therefore, the aim of the study was to asses the effect of statin and fibrate therapy (for dyslipidemia IIa and IIb, respectively) on IL-1β gene expression and monocyte release evaluated in each patient. Additionally, the effect of hypolipidemic therapy on fibrinolysis was evaluated. The study was carried out in 37 patients: 12 with biochemically confirmed type IIa dyslipidemia (treated with atorvastatin), 12 with type IIb dyslipidemia (treated with fenofibrate), and 13 age- and sex-matched normolipidemic persons (control). IL-1β concentrations in cultured monocytes and PAI-1 (Plasminogen Activator Inhibitor) plasma levels were measured using the ELISA method. To evaluate the expression of IL-1β gene in monocytes, a semiquarititive RT-PCR procedure was performed. The results were normalized with the expression of glyceraldehyde-3-phosphate dehydrogemase (GAPDH) as a housekeeping gene. Although IL-1β monocyte release was markedly elevated in patients with atherogenic dyslip idemias, IL-1β gene expression was only slightly and nonsignificantlly higher in the studied groups versus control. We have observed significant reduction of IL-1β mRNA expression after 30-day treatment with the examined drugs (atorvastatin, 2.10 ′ 0.50 versus 1.05 ′ 0.15; P < 0.001, fenofibrate; 2.27 ′ 0.48 versus 1.23 ′ 0.27; P < 0.01). There was no significant difference between statin arid fibrate effect on IL-1β mRNA expression. Similarly, we have noticed significant reduction of IL-1β release by cultured monocytes after 30-day statin therapy (133.0 ′ 5.7 pg/mL versus 77.0 ′ 3.6 pg/mL; P < 0.01) and fibrate therapy (143.9 ′ 6.5 pg/mL versus 86.2 ′ 5.9 pg/mL; P < 0.01). Besides this antiinflammatory effect, we have observed a 30% reduction of PAI-1 plasma levels in both treated groups. In conclusion, effective 1-month hypolipidemic therapy with atorvastatin or fenofibrate diminished plasma levels of proinflammatory and procoagulatory state markers.