scholarly journals Mekanisme Kerja dan Target Molekuler Interleukin-1 receptor antagonist (Anakinra) pada Aterosklerosis

2018 ◽  
Vol 11 (2) ◽  
pp. 1
Author(s):  
M. Yulis Hamidy
Keyword(s):  
Heart Failure ◽  
Congestive Heart Failure ◽  
Receptor Antagonist ◽  
Coronary Atherosclerosis ◽  
Interleukin 1 ◽  
Type I ◽  
Endogenous Inhibitor ◽  
Interleukin 1 Receptor Antagonist ◽  
Inflammatory Molecules

Inflammation plays an important role in the development and progression of a variety of cardiovascular conditions,most notably coronary atherosclerosis and congestive heart failure. A number of inflammatory molecules have beenimplicated in these processes, including interleukin-1 (IL-1). IL-1 receptor antagonist is an endogenous inhibitor of IL-1, which competitively binds to the IL-1 type I receptor without activating it. Anakinra is a nonglycosylated, recombinantform of human IL-1ra that, like endogenous IL-1ra, competitively inhibits IL-1 by binding the IL-1 type I receptor.

scholarly journals Cloning and expression of murine interleukin-1 receptor antagonist in macrophages stimulated by colony-stimulating factor 1

Blood ◽  
1991 ◽  
Vol 78 (3) ◽  
pp. 616-623
Author(s):  
H Matsushime ◽  
MF Roussel ◽  
K Matsushima ◽  
A Hishinuma ◽  
CJ Sherr
Keyword(s):  
Receptor Antagonist ◽  
Interleukin 1 ◽  
Subtractive Hybridization ◽  
Cloning And Expression ◽  
Mouse Bone Marrow ◽  
Type I ◽  
Bacterial Cells ◽  
Colony Stimulating Factor ◽  
Interleukin 1 Receptor Antagonist ◽  
Stimulating Factor

Colony-stimulating factor 1 (CSF-1) can act on mature macrophages to modulate their production of inflammatory cytokines. A cDNA encoding the interleukin-1 receptor antagonist (IL-1Ra) was cloned by subtractive hybridization from a CSF-1-stimulated murine macrophage cell line, sequenced, and expressed in mammalian and bacterial cells. Mouse IL-1Ra is a 22-Kd glycoprotein that is 76% identical to its human counterpart, shows considerably less similarity to IL-1 alpha and IL-1 beta, and competes with IL-1 alpha for binding to the type I IL-1 receptor normally expressed on T cells and fibroblasts. CSF-1 treatment of mouse bone marrow-derived macrophages led to a rapid and sustained increase in IL-1Ra mRNA during the G1 phase of the cell cycle as well as to increases in mRNAs encoding IL-1 alpha and IL-1 beta. Cycloheximide inhibited CSF-1-induced IL-1 alpha mRNA synthesis, but augmented IL-1 beta mRNA production and did not affect induction of IL- 1Ra mRNA. No IL-1Ra mRNA was observed in CSF-1-stimulated mouse fibroblasts engineered to express CSF-1 receptors, demonstrating that its regulation depends on cell context and can be dissociated from the proliferative response. In agreement, bacterial lipopolysaccharide, a nonmitogenic activator, also induced IL-1Ra and IL-1 mRNAs in macrophages. Unlike IL-1 alpha and beta, IL-1Ra contains a signal peptide. The kinetics of its induction and its ability to gain access to the secretory compartment imply that IL-1Ra may be secreted more efficiently than IL-1, and suggest that macrophages both positively and negatively regulate the IL-1 response.

scholarly journals Cloning and expression of murine interleukin-1 receptor antagonist in macrophages stimulated by colony-stimulating factor 1

Blood ◽  
1991 ◽  
Vol 78 (3) ◽  
pp. 616-623 ◽  
Author(s):  
H Matsushime ◽  
MF Roussel ◽  
K Matsushima ◽  
A Hishinuma ◽  
CJ Sherr
Keyword(s):  
Receptor Antagonist ◽  
Interleukin 1 ◽  
Subtractive Hybridization ◽  
Cloning And Expression ◽  
Mouse Bone Marrow ◽  
Type I ◽  
Bacterial Cells ◽  
Colony Stimulating Factor ◽  
Interleukin 1 Receptor Antagonist ◽  
Stimulating Factor

Abstract Colony-stimulating factor 1 (CSF-1) can act on mature macrophages to modulate their production of inflammatory cytokines. A cDNA encoding the interleukin-1 receptor antagonist (IL-1Ra) was cloned by subtractive hybridization from a CSF-1-stimulated murine macrophage cell line, sequenced, and expressed in mammalian and bacterial cells. Mouse IL-1Ra is a 22-Kd glycoprotein that is 76% identical to its human counterpart, shows considerably less similarity to IL-1 alpha and IL-1 beta, and competes with IL-1 alpha for binding to the type I IL-1 receptor normally expressed on T cells and fibroblasts. CSF-1 treatment of mouse bone marrow-derived macrophages led to a rapid and sustained increase in IL-1Ra mRNA during the G1 phase of the cell cycle as well as to increases in mRNAs encoding IL-1 alpha and IL-1 beta. Cycloheximide inhibited CSF-1-induced IL-1 alpha mRNA synthesis, but augmented IL-1 beta mRNA production and did not affect induction of IL- 1Ra mRNA. No IL-1Ra mRNA was observed in CSF-1-stimulated mouse fibroblasts engineered to express CSF-1 receptors, demonstrating that its regulation depends on cell context and can be dissociated from the proliferative response. In agreement, bacterial lipopolysaccharide, a nonmitogenic activator, also induced IL-1Ra and IL-1 mRNAs in macrophages. Unlike IL-1 alpha and beta, IL-1Ra contains a signal peptide. The kinetics of its induction and its ability to gain access to the secretory compartment imply that IL-1Ra may be secreted more efficiently than IL-1, and suggest that macrophages both positively and negatively regulate the IL-1 response.

scholarly journals Interleukin-1 Receptor Antagonist Genotype Is Associated With Coronary Atherosclerosis in Patients With Type 2 Diabetes

Diabetes ◽  
2002 ◽  
Vol 51 (12) ◽  
pp. 3582-3585 ◽  
Author(s):  
R. Marculescu ◽  
G. Endler ◽  
M. Schillinger ◽  
N. Iordanova ◽  
M. Exner ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Receptor Antagonist ◽  
Coronary Atherosclerosis ◽  
Interleukin 1 ◽  
Interleukin 1 Receptor Antagonist

Recombinant Interleukin-1 receptor antagonist for the treatment of ST-segment elevation acute myocardial infarction prevents future heart failure events: a pooled analysis of the VCUART program

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
B Van Tassell ◽  
G.F Wohlford ◽  
A.C Ho ◽  
A Vecchie ◽  
C Garmendia ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Inflammatory Response ◽  
Receptor Antagonist ◽  
Interleukin 1 ◽  
Pooled Analysis ◽  
Funding Source ◽  
St Segment Elevation ◽  
Interleukin 1 Receptor Antagonist ◽  
St Segment

Abstract Background ST segment elevation myocardial infarction (STEMI) is associated with an intense acute inflammatory response and an increased risk of death and heart failure (HF). We analyzed the effect of recombinant interleukin-1 receptor antagonist (anakinra) 100 mg subcutaneous injection given once or twice daily for 14 days on the occurrence of HF in a pooled analysis of 3 clinical trials. Methods Enrollment criteria and study procedures were the same across the three studies. High-sensitivity C-reactive protein (CRP) was measured at baseline, 72 hours, and 14 days to construct an area under the curve (AUC0–14). Clinical events up to 1 year were adjudicated by an independent committee blinded to treatment allocation. Data for anakinra once daily and anakinra twice daily were pooled into a single anakinra group. CRP data are presented as median and interquartile range to allow for deviation from Gaussian distribution and non-parametric tests were used to evaluate differences between groups. Kaplan-Meier survival analyses were conducted and the intervention groups were compared using a log-rank test. Results Between 2008 and 2017, 139 patients with STEMI were enrolled. 84 patients were randomized to anakinra and 55 patients were randomized to placebo. Anakinra significantly reduced the CRP AUC0–14 (76 [42–147] vs 222 [117–339] mg*day/L; P<0.001), the composite of death or HF hospitalization (Chi2=7.167; P=0.007), and the composite of death or new onset HF (Chi2=9.43; P=0.002) compared with placebo. Treatment with anakinra had no effect on ischemic events (composite of death, myocardial infarction, and unstable angina; (Chi2=0.574; P=0.45) or the composite of death, myocardial infarction and cerebrovascular accident (Chi2=0.065; P=0.80). Patients receiving anakinra had increased injection site reactions (20.2% vs 3.6%; P=0.005) but no change in infections (14.3% vs 9.1%, P=0.435) versus placebo. Conclusions Treatment with anakinra for 14 days following STEMI blunts the inflammatory response and appears to reduce the occurrence of HF events at 1 year. These results support the hypothesis that early and targeted modification of the inflammatory response in STEMI may be a viable strategy to improve patient outcomes. Adjudicated events at 1 year Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): National Heart Lung and Blood Institute (USA), American Heart Association (USA)

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