Cardiovascular diabetology in the core of a novel interleukins classification: the bad, the good and the aloof

被引:32
作者
Fisman, Enrique Z. [1 ,2 ]
Motro, Michael [2 ]
Tenenbaum, Alexander [1 ,2 ]
机构
[1] Chaim Sheba Med Ctr, Cardiac Rehabil Inst, IL-52621 Tel Hashomer, Israel
[2] Tel Aviv Univ, Sackler Fac Med, IL-69978 Tel Aviv, Israel
关键词
Atherosclerosis; Coronary artery disease; Cytokines; Diabetes mellitus; Interleukins;
D O I
10.1186/1475-2840-2-11
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background: The impressive correlation between cardiovascular disease and glucose metabolism alterations has raised the likelihood that atherosclerosis and type 2 diabetes may share common antecedents. Inflammation is emerging as a conceivable etiologic mechanism for both. Interleukins are regulatory proteins with ability to accelerate or inhibit inflammatory processes. Presentation of the hypothesis: A novel interleukins classification is described, based on their role in diabetes and atherosclerosis, hypothesizing that each interleukin (IL) acts on both diseases in the same direction - regardless if harmful, favorable or neutral. Testing the hypothesis: The 29 known interleukins were clustered into three groups: noxious (the "bad", 8 members), comprising IL-1, IL-2, IL-6, IL-7, IL-8, IL-15, IL-17 and IL-18; protective (the "good", 5 members), comprising IL-4, IL-10, IL-11, IL-12 and IL-13; and "aloof", comprising IL-5, IL-9, IL-14, IL-16 and IL-19 through IL-29 (15 members). Each group presented converging effects on both diseases. IL-3 was reluctant to clustering. Implications: These observations imply that 1) favorable effects of a given IL on either diabetes or atherosclerosis predicts similar effects on the other; 2) equally, harmful IL effects on one disease can be extrapolated to the other; and 3) absence of influence of a given IL on one of these diseases forecasts lack of effects on the other. These facts further support the unifying etiologic theory of both ailments, emphasizing the importance of a cardiovascular diabetologic approach to interleukins for future research. Pharmacologic targeting of these cytokines might provide an effective means to simultaneously control both atherosclerosis and diabetes.
引用
收藏
页数:10
相关论文
共 80 条
[21]  
Freeman DJ, 2001, CIRCULATION, V103, P357
[22]   Functional IL-18 is produced by primary pancreatic mouse islets and NIT-1 beta cells and participates in the progression towards destructive insulitis [J].
Frigerio, S ;
Holländer, GA ;
Zumsteg, U .
HORMONE RESEARCH, 2002, 57 (3-4) :94-104
[23]   MECHANISMS LEADING TO MYOCARDIAL-INFARCTION - INSIGHTS FROM STUDIES OF VASCULAR BIOLOGY [J].
FUSTER, V .
CIRCULATION, 1994, 90 (04) :2126-2146
[24]   New interleukins: are there any more? [J].
Gadina, M ;
Ferguson, PR ;
Johnston, JA .
CURRENT OPINION IN INFECTIOUS DISEASES, 2003, 16 (03) :211-217
[25]   MCP-1 and IL-8 trigger firm adhesion of monocytes to vascular endothelium under flow conditions [J].
Gerszten, RE ;
Garcia-Zepeda, EA ;
Lim, YC ;
Yoshida, M ;
Ding, HA ;
Gimbrone, MA ;
Luster, AD ;
Luscinskas, FW ;
Rosenzweig, A .
NATURE, 1999, 398 (6729) :718-723
[26]   Diabetes and cardiovascular disease - A statement for healthcare professionals from the American Heart Association [J].
Grundy, SM ;
Benjamin, IJ ;
Burke, GL ;
Chait, A ;
Eckel, RH ;
Howard, BV ;
Mitch, W ;
Smith, SC ;
Sowers, JR .
CIRCULATION, 1999, 100 (10) :1134-1146
[27]   Interleukin-10 protects nitric oxide-dependent relaxation during diabetes - Role of superoxide [J].
Gunnett, CA ;
Heistad, DD ;
Faraci, FM .
DIABETES, 2002, 51 (06) :1931-1937
[28]   Effect of rosiglitazone treatment on nontraditional markers of cardiovascular disease in patients with type 2 diabetes mellitus [J].
Haffner, SM ;
Greenberg, AS ;
Weston, WM ;
Chen, HZ ;
Williams, K ;
Freed, MI .
CIRCULATION, 2002, 106 (06) :679-684
[29]   Effect of angiotensin-converting-enzyme inhibition compared with conventional therapy on cardiovascular morbidity and mortality in hypertension:: the Captopril Prevention Project (CAPPP) randomised trial [J].
Hansson, L ;
Lindholm, LH ;
Niskanen, L ;
Lanke, J ;
Hedner, T ;
Niklason, A ;
Luomanmäki, K ;
Dahlöf, B ;
de Faire, U ;
Mörlin, C ;
Karlberg, BE ;
Wester, PO ;
Björck, JE .
LANCET, 1999, 353 (9153) :611-616
[30]   Associations of elevated interleukin-6 and C-reactive protein levels with mortality in the elderly [J].
Harris, TB ;
Ferrucci, L ;
Tracy, RP ;
Corti, MC ;
Wacholder, S ;
Ettinger, WH ;
Heimovitz, H ;
Cohen, HJ ;
Wallace, R .
AMERICAN JOURNAL OF MEDICINE, 1999, 106 (05) :506-512