Interleukin-1 receptor antagonist as a modulator of gender differences in the febrile response to lipopolysaccharide in rats

2007 ◽  
Vol 292 (4) ◽  
pp. R1667-R1674 ◽  
Author(s):  
H. Ashdown ◽  
S. Poole ◽  
P. Boksa ◽  
G. N. Luheshi
Keyword(s):  
Receptor Antagonist ◽  
Plasma Levels ◽  
Physiological State ◽  
Interleukin 1 ◽  
Female Rats ◽  
Male Rats ◽  
Mrna Levels ◽  
Febrile Response ◽  
Interleukin 1 Receptor Antagonist ◽  
Near Term

Febrile responses to bacterial pathogens are attenuated near term of pregnancy in several mammalian species. It is unknown, however, whether this reflects a fundamental physiological adaptation of female rats or whether it is specific to pregnancy. The aims of this study therefore were 1) to determine whether febrile responses to the bacterial endotoxin lipopolysaccharide (LPS) are attenuated in female vs. male rats and, if so, to identify possible mechanisms involved in modulating this and 2) to assess whether plasma concentrations of the anti-inflammatory cytokine, interleukin-1 receptor antagonist (IL-1ra), an important regulator of fever, are dependent on the physiological state of the female and could therefore be involved in modulating febrile responses. We found febrile responses were attenuated in cycling female vs. male rats and also in near-term pregnant dams vs. cycling females after intraperitoneal injection of LPS (0.05 mg/kg). Plasma levels of IL-1ra were significantly greater in female rats after injection of LPS, particularly during pregnancy, than in males. This was accompanied by attenuated levels of hypothalamic IL-1β and cyclooxygenase-2 mRNA, two key mediators of the febrile response, in female rats. Furthermore, increasing plasma levels of IL-1ra in male rats by intraperitoneal administration of the recombinant antagonist attenuated hypothalamic mRNA levels of these mediators after LPS. These data suggest that there is a fundamental difference in febrile response to LPS between the genders that is likely regulated by IL-1ra. This may be an important mechanism that protects the developing fetus from potentially deleterious consequences of maternal fever during pregnancy.

THE EFFECTS OF HUMAN RECOMBINANT INTERLEUKIN-1 RECEPTOR ANTAGONIST (IL-1ra) ON PLASMA LEVELS OF PROSTAGLANDINS AND LEUKOTRIENES IN SEPTIC PATIENTS

1994 ◽  
Vol 22 (1) ◽  
pp. A193 ◽  
Author(s):  
Bruce Friedman ◽  
Anthony Mure ◽  
Collin Brathwaite ◽  
James Quinn ◽  
Eugenia Shapiro ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Plasma Levels ◽  
Interleukin 1 ◽  
Interleukin 1 Receptor Antagonist

Haplotypes of the interleukin-1 receptor antagonist gene, interleukin-1 receptor antagonist mRNA levels and the risk of myocardial infarction

2009 ◽  
Vol 203 (1) ◽  
pp. 201-205 ◽  
Author(s):  
Rick van Minkelen ◽  
Stephanie Bezzina Wettinger ◽  
Marieke C.H. de Visser ◽  
Hans L. Vos ◽  
Pieter H. Reitsma ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Receptor Antagonist ◽  
Interleukin 1 ◽  
Mrna Levels ◽  
Interleukin 1 Receptor Antagonist

Interleukin-1 receptor antagonist: effectiveness against interleokin-1 fever

1992 ◽  
Vol 70 (12) ◽  
pp. 1590-1596 ◽  
Author(s):  
Flavio Coceani ◽  
Jodi Lees ◽  
Jane Redford ◽  
Isis Bishai
Keyword(s):  
Receptor Antagonist ◽  
Bolus Injection ◽  
Third Ventricle ◽  
Interleukin 1 ◽  
Inhibitory Effect ◽  
Prostaglandin E ◽  
Febrile Response ◽  
The Third ◽  
Interleukin 1 Receptor Antagonist ◽  
Before And After

Conscious cats were used to examine the effectiveness of the interleukin-1 receptor antagonist against the fever induced by interleukin-1 and endotoxin. Although inactive by itself, the antagonist (three 1-μg bolus injections at 10-min intervals), injected into the third ventricle, attenuated the febrile response to a subsequent intracerebroventricular bolus of interleukin-1. The rise in prostaglandin E2 levels in cerebrospinal fluid, which is a characteristic feature of fever, was curtailed as well. The interleukin-1 antagonist had little or no inhibitory effect on the response to an intracerebroventricular bolus of endotoxin, even though a higher dose was employed (2-μg bolus injections given three times at 10-min intervals and six times at 30-min intervals, respectively, before and after endotoxin administration). At either dosage, the intracerebroventricular antagonist was completely ineffective against an intravenous bolus injection of interleukin-1 or endotoxin and both fever and prostaglandin E2 elevation developed unabated. We conclude that brain receptors mediating the pyrogenic action of centrally injected interleukin-1 are susceptible to the antagonist. The same receptors, however, are seemingly not activated by systemic pyrogens. Our findings are consistent with the concept of circulating interleukin-1 acting outside the blood–brain barrier in the normal sequence of fever.Key words: interleukin-1, interleukin-1 receptor antagonist, endotoxin, prostaglandin E2, fever mechanism.

Abstract 13025: Deficiency of Interleukin-1 Receptor Antagonist Promotes Angiotensin II-induced Aortic Inflammation and Aneurysm

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Koji Akita ◽  
Kikuo Isoda ◽  
Sarasa Isobe ◽  
Tomiharu Niida ◽  
Hiroyuki Daida
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Systolic Blood Pressure ◽  
Receptor Antagonist ◽  
Abdominal Aorta ◽  
Interleukin 1 ◽  
Mrna Levels ◽  
Interleukin 1 Receptor Antagonist ◽  
Abdominal Aortic ◽  
Tnf Α

Introduction: Angiotensin II (AngII) increases arterial pressure and induces inflammation. Although interleukin-1 receptor antagonist (IL-1Ra) is one of the most important anti-inflammatory cytokines, the role of IL-1Ra in AngII-induced aortic inflammation and aneurysm remains unknown. Methods and Results: To determine the contrition of IL-1Ra to AngII-induced aortic inflammation, male wild-type (WT) (n=18) and IL-1Ra-deficient (IL-1Ra-/-) (n=18) mice were infused with AngII (3000ng/kg per minute) using subcutaneous osmotic pumps for 28 days. 7 days after infusion, real-time PCR of abdominal aorta in IL-1Ra-/- mice revealed significantly increased mRNA levels of IL-6 (2.1-fold, p<0.01), TNF-α (4.1-fold, p<0.01), and MMP-9 (20.3-fold, p<0.05) compared with WT mice. 14 days after infusion, both systolic blood pressure (178±21 vs 135±21 mmHg, p<0.01)and abdominal aortic width (1.02±0.12 vs 0.82±0.05 mm, p<0.01) in IL-1Ra-/- mice significantly increased compared with WT mice. Moreover, AngII infusion into IL-1Ra-/- mice also led to a significant increased occurrence of fatal aortic rupture (IL-1Ra-/-: 89% vs WT: 6%, p<0.01). Next, WT (n=6) and IL-1Ra-/- (n=6) mice were infuse with AngII for only 14 days, and histological analyses were performed at 28 days after operation. Interestingly, the abdominal aortic width in IL-1Ra-/- mice more significantly increased than those in WT mice (1.57±0.34 vs 0.80±0.04 mm, p<0.01), although IL-1Ra-/- and WT mice did not differ with regard to systolic blood pressure (105±15 vs 109±13 mmHg, p=0.61) at 28 days after operation. Histological analyses revealed there were numerous inflammatory cells around the abdominal aorta in IL-1Ra-/- mice, but not in WT mice. Furthermore, elastin staining showed destruction of the elastic lamina of abdominal aorta in IL-1Ra-/- mice. TNF-α protein expression also increased significantly in IL-1Ra-/- mice compared to WT mice at 28days. Conclusions: The present study shows that IL-1Ra deficiency in mice led to increase inflammation and the development of aortic aneurysm after AngII infusion. Furthermore, our results also showed IL-1Ra deficiency continued the AngII-induced inflammation even though blood pressure was improved after cessation of AngII infusion.

scholarly journals Inflammatory Bone Loss in Experimental Periodontitis Induced by Aggregatibacter actinomycetemcomitans in Interleukin-1 Receptor Antagonist Knockout Mice

2014 ◽  
Vol 82 (5) ◽  
pp. 1904-1913 ◽  
Author(s):  
A. Izawa ◽  
Y. Ishihara ◽  
H. Mizutani ◽  
S. Kobayashi ◽  
H. Goto ◽  
...  
Keyword(s):  
Bone Loss ◽  
Periodontal Disease ◽  
Receptor Antagonist ◽  
Mrna Expression ◽  
Interleukin 1 ◽  
Aggregatibacter Actinomycetemcomitans ◽  
Mrna Levels ◽  
Content Type ◽  
Interleukin 1 Receptor Antagonist ◽  
Experimental Periodontitis

ABSTRACTThe interleukin-1 receptor antagonist (IL-1Ra) binds to IL-1 receptors and inhibits IL-1 activity. However, it is not clear whether IL-1Ra plays a protective role in periodontal disease. This study was undertaken to compare experimental periodontitis induced byAggregatibacter actinomycetemcomitansin IL-1Ra knockout (KO) mice and wild-type (WT) mice. Computed tomography (CT) analysis and hematoxylin-and-eosin (H&E) and tartrate-resistant acid phosphatase (TRAP) staining were performed. In addition, osteoblasts were isolated; the mRNA expression of relevant genes was assessed by real-time quantitative PCR (qPCR); and calcification was detected by Alizarin Red staining. Infected IL-1Ra KO mice exhibited elevated (P, <0.05) levels of antibody againstA. actinomycetemcomitans, bone loss in furcation areas, and alveolar fenestrations. Moreover, protein for tumor necrosis factor alpha (TNF-α) and IL-6, mRNA for macrophage colony-stimulating factor (M-CSF), and receptor activator of NF-κB ligand (RANKL) in IL-1Ra KO mouse osteoblasts stimulated withA. actinomycetemcomitanswere increased (P, <0.05) compared to in WT mice. Alkaline phosphatase (ALP), bone sialoprotein (BSP), osteocalcin (OCN)/bone gla protein (BGP), and runt-related gene 2 (Runx2) mRNA levels were decreased (P, <0.05). IL-1α mRNA expression was increased, and calcification was not observed, in IL-1 Ra KO mouse osteoblasts. In brief, IL-1Ra deficiency promoted the expression of inflammatory cytokines beyond IL-1 and altered the expression of genes involved in bone resorption inA. actinomycetemcomitans-infected osteoblasts. Alterations consistent with rapid bone loss in infected IL-Ra KO mice were also observed for genes expressed in bone formation and calcification. In short, these data suggest that IL-1Ra may serve as a potential therapeutic drug for periodontal disease.

Interleukin 1-receptor antagonist blocks interleukin 1-induced sleep and fever

1991 ◽  
Vol 260 (2) ◽  
pp. R453-R457 ◽  
Author(s):  
M. R. Opp ◽  
J. M. Krueger
Keyword(s):  
Receptor Antagonist ◽  
Eye Movement ◽  
Brain Temperature ◽  
Interleukin 1 ◽  
Central Administration ◽  
Rapid Eye Movement Sleep ◽  
Febrile Response ◽  
Purification And Characterization ◽  
Interleukin 1 Receptor Antagonist

The recent purification and characterization of an interleukin 1-receptor antagonist (IL-1ra) has provided an additional means of elucidating the mechanisms involved in the responses initiated by IL-1. Central administration of IL-1 to rabbits results in a characteristic febrile response and in increased non-rapid-eye-movement sleep (NREMS). In this study, rabbits received various doses of IL-1ra (10-1,000 micrograms) or pyrogen-free saline intracerebroventricularly, and sleep-wake activity and brain temperature (Tbr) were determined for the next 24 h. All doses of IL-1ra tested tended to reduce NREMS in the first postinjection hour with little effect on Tbr. When rabbits were pretreated with 100 micrograms IL-1ra and then injected with 10 ng IL-1, the characteristic IL-1-induced febrile and NREMS-promoting effects were completely blocked.

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