Interleukin-1 Receptor Antagonist Knockout Mice Have An Increased Acute Inflammatory Response In The Lung After LPS Exposure

2011 ◽  
Author(s):  
Kristin M. Hudock ◽  
Yuhong Liu ◽  
G. Scott Worthen
Keyword(s):  
Inflammatory Response ◽  
Receptor Antagonist ◽  
Knockout Mice ◽  
Interleukin 1 ◽  
Acute Inflammatory Response ◽  
Interleukin 1 Receptor Antagonist

scholarly journals Features of cytokine profile in patients with local and generalized soft tissue infections

2013 ◽  
Vol 94 (4) ◽  
pp. 455-459
Author(s):  
N A Barkhatova
Keyword(s):  
Tumor Necrosis Factor ◽  
Inflammatory Response ◽  
Receptor Antagonist ◽  
Tumor Necrosis Factor Alpha ◽  
Tumor Necrosis ◽  
Interleukin 1 ◽  
Necrosis Factor Alpha ◽  
Interleukin 1 Receptor Antagonist ◽  
Factor Alpha ◽  
Necrosis Factor

Aim. To determine the features of cytokine profile in patients with local and generalized soft tissue infections. Methods. The treatment results of 2350 patients with soft tissues infections since 1998 to 2012 were analyzed. ELISA test was used to measure tumor necrosis factor alpha and interleukin-1 receptor antagonist levels in 300 randomly picked patients with local (75 patients, comparison group) and generalized (225 patients, main group) forms of soft tissue infections. Results. In patients with generalized infections, tumor necrosis factor alpha level was 1.5 times higher in patients with mild systemic inflammatory response, 3.5 times higher - in patients with moderate and 6.7 times higher in patients with severe systemic inflammatory response compared to healthy controls. Interleukin-1 receptor antagonist levels were also elevated and related to the degree of inflammatory response, thus, it was the highest (2 times higher compared to controls) in patients with moderate systemic inflammatory response, while in patients with mild and severe inflammation it was only 30-40% higher. The significant increase in tumor necrosis factor alpha level associated with normal interleukin-1 receptor antagonist level is characteristic for different forms of sepsis. At the same time, increase in interleukin-1 receptor antagonist level associated with minimal changes in tumor necrosis factor alpha level can be used as a diagnostic criteria for compensated inflammatory response I patients with local infections cytokine profile was normal. The severity of systemic inflammation and clinical course of generalized infection depended not only on the absolute increase of cytokine levels, but on pro-inflammatory (tumor necrosis factor alpha) and anti-inflammatory (interleukin-1 receptor antagonist) cytokine levels misbalance. Conclusion. Examining the serum cytokine levels allows to confirm the diagnosis of generalized infection on early stages and to differentiate between compensated and non-ompensated systemic inflammatory response.

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)

scholarly journals Attenuation of Ischemic Inflammatory Response in Mouse Brain Using an Adenoviral Vector to Induce Overexpression of Interleukin-1 Receptor Antagonist

1998 ◽  
Vol 18 (8) ◽  
pp. 840-847 ◽  
Author(s):  
Guo-Yuan Yang ◽  
Xiao-Hong Liu ◽  
Chitoshi Kadoya ◽  
Yong-Jie Zhao ◽  
Ying Mao ◽  
...  
Keyword(s):  
Brain Injury ◽  
Basal Ganglia ◽  
Inflammatory Response ◽  
Receptor Antagonist ◽  
Adenoviral Vector ◽  
Interleukin 1 ◽  
Saline Control ◽  
Ischemic Brain Injury ◽  
Ischemic Brain ◽  
Interleukin 1 Receptor Antagonist

It has been demonstrated that administration of an interleukin-1 receptor antagonist protein (IL-1ra) reduces ischemic brain injury; however, the detrimental mechanism initiated by interleukin-1 (IL-1) in ischemic brain injury is unclear. In this study, we used mice that were transfected to overexpress human IL-1ra to elucidate the role of IL-1 in the activation of the inflammatory response after middle cerebral artery occlusion (MCAO). Myeloperoxidase (MPO) activity and immunohistostaining were used as a marker of polymorphonuclear leukocytes (PMNL) infiltration. Adenoviral vector (1 × 109 particles) was administered by injection into the right lateral ventricle in mice. Five days later, MCAO was performed on the mice using a suture technique. Permanent MCAO was achieved for 24 hours in the Ad.RSV IL-1ra-transfected, Ad.RSV lacZ-transfected, and saline (control) mice. Myeloperoxidase activity was quantified in each region and localization of MPO was determined by immunohistochemistry. After 2 hours of MCAO, the surface cerebral blood flow was reduced to 13.5% ± 3.4%, 10.75% ± 2.6%, and 10.9% ± 2.6% of baseline in the ischemic hemisphere in Ad.RSV IL-1ra-transfected, Ad.RSV- lacZ-transfected, and saline-treated mice, respectively. The MPO activity in the ischemic hemisphere in the Ad.RSV lacZ group was similar to that in the saline control group (cortex: 0.40 ± 0.22 versus 0.33 ± 0.11; basal ganglia: 0.46 ± 0.23 versus 0.49 ± 0.17; P > 0.05); however, it was significantly reduced in the Ad.RSV IL-1ra group (cortex: 0.18 ± 0.07; basal ganglia: 0.26 ± 0.15; P < 0.05). Myeloperoxidase immunohistochemistry showed that the massive accumulation of MPO-positive cells in the ischemic cortex, striatum, and corpus callosum regions was greatly attenuated in Ad.RSV IL-1ra-transfected mice. Our results indicate that Ad.RSV IL-1ra-transfected mice provide a useful tool to study the mechanism of action of IL-1. The MPO activity assay and immunostaining after 24 hours of focal ischemia were significantly reduced in IL-1ra gene-transfected mice, suggesting that IL-1 may play an important role in the activation of inflammatory cells during focal cerebral ischemia.

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