Early interleukin-1 receptor antagonist elevation in patients with acute myocardial infarction

Patti, Giuseppe; D’Ambrosio, Andrea; Mega, Simona; Giorgi, Gabriele; Zardi, Enrico Maria; Zardi, Domenico Maria; Dicuonzo, Giordano; Dobrina, Aldo; Sciascio, Germano Di

doi:10.1016/j.jacc.2003.07.032

Cited by 43 publications

(32 citation statements)

References 16 publications

(15 reference statements)

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“…IL-1Ra is an acute reactive protein and has been found to be prominently expressed at an early stage of acute myocardial infarction. 23) However, our data revealed that serum IL-1Ra levels were not correlated to either the CRP levels or the morphology of coronary plaque in patients with stable CAD.…”

Section: Discussioncontrasting

confidence: 62%

Serum Interleukin-6 Levels, Not Genotype, Correlate With Coronary Plaque Complexity

et al. 2008

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SUMMARYAn increased serum interleukin-6 (IL-6) level is associated with an increased risk of cardiovascular events in healthy subjects. However, it is unknown whether the level of serum IL-6 or genetic IL-6 polymorphism is correlated with the complexity of coronary plaque in patients with stable coronary artery disease (CAD).Patients with stable CAD (n = 135) were divided into 3 groups: insignificant coronary plaque (n = 77), simple coronary plaque (n = 15), and complex coronary plaque (n = 43). IL-6-174G > C polymorphism and serum levels of IL-6 and C-reactive protein (CRP) were investigated.No significant difference in the distribution of IL-6 genotypes was found among the groups. The presence of complex coronary plaque was associated with higher serum concentrations of IL-6 (P = 0.026) and CRP (P < 0.0001). To predict the presence of complex lesions, IL-6 > 5.8 ng/L and CRP > 2.6 mg/L had sensitivities of 86% and 74%, and specificities of 61% and 62%, respectively. By multivariate analysis, IL-6 > 5.8 ng/L and CRP > 2.6 mg/L were independently related to the presence of complex coronary plaque (P = 0.0002 and 0.004, respectively). IL-6 > 5.8 ng/L and CRP > 2.6 mg/L were associated with a 4.5-fold increase in the odds of having complex coronary plaque (P < 0.005).A simple measurement of the serum IL-6 level in patients with CAD can potentially identify subjects with complex coronary lesions and provide the option of aggressive medical strategies in a clinical setting. (Int Heart J 2008; 49: 391-402)

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Section: Discussioncontrasting

confidence: 62%

Serum Interleukin-6 Levels, Not Genotype, Correlate With Coronary Plaque Complexity

et al. 2008

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“…7 Its levels are elevated early in patients presenting with ST-segment-elevation AMI, 5 and the greater the area of myocardium at risk is, the greater the increase in IL-1Ra levels is. 6 Moreover, in observational studies, higher IL-1Ra levels in patients with acute coronary syndromes were associated with unfavorable outcome.…”

Section: Il-1ra In Amimentioning

confidence: 99%

“…3,4 Like other acute-phase reactants, IL-1Ra levels increase during AMI, and its levels correlate with prognosis. 5,6 The role of increasing IL-1Ra during AMI is unclear, and speculations have been made that its role ranges from merely a marker of damage to a modulator of the inflammatory response to a potential cytoprotective agent. 5,8 Recently, forced expression of IL-1Ra in an animal model has been shown to be cardioprotective in terms of reduced infarct size and apoptosis.…”

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confidence: 99%

Anakinra, a Recombinant Human Interleukin-1 Receptor Antagonist, Inhibits Apoptosis in Experimental Acute Myocardial Infarction

et al. 2008

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Background-Experimental interleukin-1 receptor antagonist gene overexpression has shown that interleukin-1 receptor antagonist is cardioprotective during global cardiac ischemia. The aim of the present study was to test the impact of an exogenous recombinant human interleukin-1 receptor antagonist (anakinra) in experimental acute myocardial infarction. Methods and Results-Two animal studies were conducted: one of immediate anakinra administration during ischemia in the mouse and one of delayed anakinra administration 24 hours after ischemia in the rat. Seventy-eight Institute of Cancer Research mice and 20 Wistar rats underwent surgical coronary artery ligation (or sham operation) and were treated with either anakinra 1 mg/kg or NaCl 0.9% (saline). Treatment was administered during surgery and then daily for 6 doses in the mice and starting on day 2 daily for 5 doses in the rats. Twenty-eight mice underwent infarct size assessment 24 hours after surgery, 6 saline-treated mice and 22 mice treated with increasing doses of anakinra (1 mg/kg [nϭ6], 10 mg/kg [nϭ6], and 100 mg/kg [nϭ10]); 6 mice were euthanized at 7 days for protein expression analysis. The remaining animals underwent transthoracic echocardiography before surgery and 7 days later just before death. Cardiomyocyte apoptosis was measured in the peri-infarct regions. The antiapoptotic effect of anakinra was tested in a primary rat cardiomyocyte culture during simulated ischemia and in vitro on caspase-1 and -9 activities. At 7 days, 15 of the 16 mice (94%) treated with anakinra were alive versus 11 of the 20 mice (55%) treated with saline (Pϭ0.013).No differences in infarct size at 24 hours compared with saline were observed with the 1-and 10-mg/kg doses, whereas a 13% reduction in infarct size was found with the 100-mg/kg dose (Pϭ0.015). Treatment with anakinra was associated with a significant reduction in cardiomyocyte apoptosis in both the immediate and delayed treatment groups (3.1Ϯ0.2% versus 0.5Ϯ0.3% [PϽ0.001] and 4.2Ϯ0.4% versus 1.1Ϯ0.2% [PϽ0.001], respectively). Compared with saline-treated animals, anakinra-treated mice and rats showed signs of more favorable ventricular remodeling. In vitro, anakinra significantly prevented apoptosis induced by simulated ischemia and inhibited caspase-1 and -9 activities. Conclusions-Administration of anakinra within 24 hours of acute myocardial infarction significantly ameliorates the remodeling process by inhibiting cardiomyocyte apoptosis in 2 different experimental animal models of AMI. This may open the door for using anakinra to prevent postischemic cardiac remodeling and heart failure.

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“…15 Indeed, because of its early release at sites of ruptured plaque, even before myocardial necrosis has occurred, IL-1ra was found to be elevated in patients presenting with ST-segment elevation myocardial infarction earlier than traditional markers of necrosis. 16 …”

Section: Cardiac-related Effects Of Il-1 and Il-1ramentioning

confidence: 99%

Inflammation and Cardiovascular Disease

Fearon

2008

Circulation

140

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Early interleukin-1 receptor antagonist elevation in patients with acute myocardial infarction

Cited by 43 publications

References 16 publications

Serum Interleukin-6 Levels, Not Genotype, Correlate With Coronary Plaque Complexity

Serum Interleukin-6 Levels, Not Genotype, Correlate With Coronary Plaque Complexity

Anakinra, a Recombinant Human Interleukin-1 Receptor Antagonist, Inhibits Apoptosis in Experimental Acute Myocardial Infarction

Inflammation and Cardiovascular Disease

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