Effect Of Cilazapril On Cytokines Network Regulation And Cardiac Function In The Patients With Congestive Heart Failure

Objective:To observe the change of serum levels of cytokines in the patients with congestive heart failure(CHF),and to investigate the effect of Cilazapril on relguating the cytokines network and improving the cardiac function in the patients with CHF.Methods:100 patients with CHF(CHF group)and 50 healthy physical examinations(control group)were selected,and the serum levels of interleukin-6(IL-6),interleukin-8(IL-8),interleukin- 10(IL-10)and tumour necrosis factor-α(TNF-α)concentrations were measured using cytometric bead array(CBA)protein array system.Patients with CHF were divided randomly into Cilazapril group or general treatment group for 12 weeks.The general treatment group was given to the CHF general treatment.Besides this therapy,Cilazapril was titrated from low dose to maximal tolerance dose in Cilazapril group.Serum levels of IL-6,IL-8, IL-10 and TNF-α,and the echocardiography[left ventricular ejection fraction(LVEF),left ventricular end-diastolic diameter(LVEDD),cardiac output(CO)and fractional shortening(FS)]were measured in the patients with CHF before and after 12 weeks treatment.In the control group,only the serum levels of IL-6,IL-8,IL-10 and TNF-αwere measured.Results:1.The main findings in the CHF group were:(1)Both the serum levels of IL-6,IL-8,IL-10 and TNF-αwere significantly higher than those in the control group[IL-6:(11.74±12.78)pg/ml vs.(4.19±2.46)pg/ml, P＜0.01;IL-8:(41.96±45.24)pg/ml vs.(15.98±8.52)pg/ml,P＜0.01;IL-10: (14.84±11.39)pg/ml vs.(2.99±3.08)pg/ml,P＜0.01;TNF-α:(9.58±5.60) pg/ml vs.(6.28±1.41)pg/ml,P＜0.01];The serum levels of IL-8 were higher in the serious NYHA group[NYHAⅣ:(60.71±65.89)pg/ml vs. NYHAⅡ:(33.48±26.00)pg/ml,P＜0.05].(2)The serum levels of IL-8,10 and TNF-αwere positively related to each other(IL-8 vs.TNF-αr=0.229 P＜0.05;IL-8 vs.IL-10 r=0.218 P＜0.05;TNF-αvs.IL-10 r=0.420 P＜0.01). (3)The ratios of IL-8/IL-10 and TNF-α/IL-10 in the CHF group were higher in the serious NYHA groups[IL-8/ IL-10:(8.29±11.18)vs. (3.35±3.90),P＜0.01;TNF-α/IL-10:(1.78±3.13)vs.(0.77±0.49),P＜0.05]. 2.Treating interventions:currently there are 45 follow-up of patients,there are Cilazapril group(n=25)and general treatment group(n=20).The main findings in the 45 patients were:(1)In the Cilazapril group,the serum levels of IL-6,IL-8 and TNF-αwere significantly decreased[IL-6: (5.31±2.37)pg/ml vs.(13.79±10.21)pg/ml,P＜0.01;IL-8:(15.56±15.41) pg/ml vs.(177.00±294.33)pg/ml,P＜0.05;TNF-α:(8.71±4.31)pg/ml vs. (10.55±3.92)pg/ml,P＜0.05],and the serum levels of IL-6 were significantly decreased as compared with the general treatment group [(5.31±2.37)pg/ml vs.(8.94±4.30)pg/ml,P＜0.01],the serum levels of IL-10 had an upward trend[(13.03±16.77)pg/ml vs.(11.33±7.15)pg/ml, P=0.627];and the LVEF,CO,FS were significantly increased[LVEF: (45.92±12.31)%vs.(37.44±7.84)%,P＜0.01;CO:(6.78±2.39)L/min vs. (5.64±1.64)L/min,P＜0.01;FS:(25.22±8.73)%vs.(19.86±6.33)%,P＜0.01]. (2)In the control group,only LVEF and FS improved[LVEF:(47.51±8.63) %vs.(39.80±7.84)%,P＜0.01;FS:(23.52±6.42)%vs.(19.71±4.61)%, P＜0.01],cytokine levels showed no change(P＞0.05).Conclusion:There are the levels of inflammatory cytokines inadequately raised and the levels of anti-inflammatory cytokines relatively lowered in CHF patients,the imbalance in the cytokine network may be involved in development and progression of CHF.The angiotensin converting enzyme inhibiter(ACEI)could reduce the serum levels of pro-inflammatory cytokines,increase the serum levels of anti-inflammatory cytokine,and display the regulation to the cytokine network,which may improve cardiac function.