1.Thermal hyperalgesic effects induced by intracerebroventricular injection of interleukin-1beta in rats.
Guang-Chen JI ; Fei MA ; Yu-Qiu ZHANG ; Gen-Cheng WU
Acta Physiologica Sinica 2002;54(4):325-328
The present study was to investigate the effects of intracerebroventricular (i.c.v.) injection of interleukin-1beta (IL-1beta) on thermal nociception in SD rats. The rats were divided into control and drug-administration groups. The animals of control group were given vehicle solution via i.c.v. injection. The animals of drug-administered groups were given IL-1beta at different doses (5, 50 and 500 pg/kg b.w.) via i.c.v. injection. IL-1 receptor antagonist (IL-1ra, 50 ng/kg) was injected 20 min before injection of IL-1beta or vehicle solution. The nociceptive threshold, which was represented as paw withdrawal latency (PWL), to a noxious thermal stimulation was measured using an analgesiameter. I.c.v. injection of IL-1beta dose-dependently shortened the PWL. At the dose of 500 pg/kg, the shortening of the PWL occurred at 20 min, reaching a peak within 40 min, lasted 100 min after injection, then gradually returned to the baseline level. Pretreatment with IL-1ra completely blocked the effects of IL-1beta-induced shortening in PWL. The results obtained suggest that IL-1beta may induce hyperalgesia in rats through binding to IL-1 receptors in the brain.
Animals
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Hot Temperature
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Hyperalgesia
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drug therapy
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Injections, Intraventricular
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Interleukin 1 Receptor Antagonist Protein
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pharmacology
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Interleukin-1beta
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pharmacology
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Nociception
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Rats
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Rats, Sprague-Dawley
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Receptors, Interleukin-1
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antagonists & inhibitors
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metabolism
;
Touch
2.Analysis of interleukin-1 receptor antagonist gene polymorphism in Chinese patients with Alzheimer's disease.
Sheng BI ; De-Sheng WANG ; Guo-Lin LI ; Shang-Ha PAN
Chinese Medical Sciences Journal 2004;19(2):93-96
OBJECTIVETo identify an interaction between the interleukin-1 receptor antagonist gene polymorphism and risk of Alzheimer's disease.
METHODSThe study included 117 healthy controls, 85 patients with Alzheimer's disease in a Northeastern Chinese population of Han nationality. Genotypes were determined by a polymerase chain reaction amplification of the intron 2 fragment, harbouring a variable number of short tandem nucleotide sequences. Amplification products were separated on a 2% agarose gel.
RESULTSThe allele 2 frequency was 27% in healthy controls, and 21% in patients with Alzheimer's disease. Thus for allele 2 as well as for all other alleles, genotypes, or carriage rates, no significant differences compared with controls.
CONCLUSIONSNo association of interleukin-1 receptor antagonist gene polymorphism with Alzheimer's disease was identified in this population. It is also possible that the increased risk and disease modifying effects are caused by linkage disequilibrium with other genomic variants in other nearby genes.
Aged ; Alleles ; Alzheimer Disease ; genetics ; Asian Continental Ancestry Group ; China ; Female ; Gene Frequency ; Genotype ; Humans ; Introns ; Male ; Middle Aged ; Polymorphism, Genetic ; Receptors, Interleukin-1 ; antagonists & inhibitors
3.An experimental study on gene transfection of human interleukin-1 receptor antagonist gene into chondrocytes of temporomandibular joint.
Yisong LI ; Weidong TIAN ; Dong WANG
West China Journal of Stomatology 2003;21(1):19-21
OBJECTIVEThe purpose of this study was to investigate methods and expression of the recombinant human interleukin-1 receptor antagonist gene transfected into chondrocytes of temporomandibular joints (TMJ).
METHODSChondrocytes derived from the TMJ of 5-7 months old human fetus were transfected by recombinant human interleukin-1 receptor antagonist gene via cationic liposome (Lipefectine) as a medium. The expressing level of hIL-1ra protein was detected using immunocytochemistry and enzyme-linked immunosorbent assay (ELISA).
RESULTSThe positive results of the immunocytochemistry were found. The positive expression was detected in the cell plasma and the cell culture supernatant, and there was significant difference between the cells with and without gene transfection (P < 0.01).
CONCLUSIONThis feasible method provides experimented evidence for the future gene therapy of temporomandibular joint osteoarthrosis.
Chondrocytes ; cytology ; Enzyme-Linked Immunosorbent Assay ; Fetus ; Phosphatidylethanolamines ; Receptors, Interleukin-1 ; antagonists & inhibitors ; biosynthesis ; genetics ; Recombinant Proteins ; biosynthesis ; genetics ; Temporomandibular Joint ; cytology ; Transfection
4.Effects of human recombinant interleukin-1 receptor antagonist on isolated trachea smooth muscle of the guinea pig.
Xiao-qun GE ; Ji-ping LI ; Hong-quan ZHANG
Acta Pharmaceutica Sinica 2003;38(6):409-411
AIMTo study the effects of human recombinant interleukin-1 receptor antagonist (IL-1ra) on isolated trachea smooth muscle (TSM) of the guinea pig.
METHODSChanges of the tension of isolated trachea were measured by force-displacement transducer and MedLab recording system in vitro.
RESULTSIL-1ra showed direct relaxed effect on TSM in normal and ovalbumin sensitized guinea pig. The EC50 values were 8.06 x 10(-8) and 5.88 x 10(-7) mol.L-1 respectively. IL-1ra (1 x 10(-7)-1 x 10(-5) mol.L-1) concentration-dependently inhibited the contraction of TSM induced by 1 x 10(-3) mol.L-1 histamine (His), 1 x 10(-3) mol.L-1 acetylcholine (ACh) and 1 x 10(-6) mol.L-1 5-hydroxytryptamine (5-HT) (P < 0.05 or 0.01). When IL-1ra was given in advance, the contractile actions of His, ACh and 5-HT were antagonized by IL-1ra (1 x 10(-7)-1 x 10(-5) mol.L-1), the pD'2 value for His was 6.6 +/- 0.3. However, the contractile action of ACh was enhanced by IL-1ra at low concentration of 1 x 10(-9)-1 x 10(-8) mol.L-1. IL-1ra significantly prevented and inhibited the contraction of sensitized TSM induced by antigen ovalbumin, the IC50 value was 4.48 x 10(-7) mol.L-1.
CONCLUSIONThe results indicate that IL-1ra, within certain concentration, can relax the normal, contracted and sensitized ISM of the guinea pig in vitro.
Animals ; Female ; Guinea Pigs ; In Vitro Techniques ; Interleukin 1 Receptor Antagonist Protein ; Male ; Muscle Contraction ; drug effects ; Muscle, Smooth ; drug effects ; Receptors, Interleukin-1 ; antagonists & inhibitors ; Recombinant Proteins ; pharmacology ; Sialoglycoproteins ; pharmacology ; Trachea ; cytology
5.Changes of Plasma Interleukin-1 Receptor Antagonist, Interleukin-8 and other Serologic Markers during Chemotherapy in Patients with Active Pulmonary Tuberculosis.
The Korean Journal of Internal Medicine 2003;18(3):138-145
BACKGROUND: The human immune response to Mycobacterium tuberculosis is mediated by macrophages and T-lymphocytes. The alveolar macrophage phagocyting mycobacterium produces interleukin (IL) -1 as an inflammatory mediator, and IL-8 as a cytokine for leukocyte recruitment and granuloma formation. Interleukin-1 receptor antagonist (IL-1ra) is an internal antagonist of IL-1. METHODS: Plasma levels of IL-1ra and IL-8 and other serologic markers were measured in 18 patients with active tuberculosis before treatment and after 2 months and 6 months of treatment. RESULTS: During treatment with antituberculous medication, patients showed significant changes in hemoglobin, hematocrit, white blood cells (WBC), platelet, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), ferritin and plasma IL-1ra. After 2 months of treatment, ESR and CRP diminished significantly; after 6 months, hemoglobin increased while WBC, platelet, ESR, CRP and ferritin decreased significantly compared to their pre-treatment levels. There were two groups: patients with delayed therapeutic responses, and patients with early responses. At each point of observation, the former group of patients showed lower body weight and lower levels of hemoglobin and hematocrit, and higher levels of WBC, platelet, ESR, IL-8 and IL-1ra than the latter group. During the course of the treatment, we observed considerable differences in body weight, body mass index, hemoglobin, hematocrit, WBC and platelet counts, ESR, CRP and ferritin in both the early-response and delayed-response groups. CONCLUSION: We believe that the plasma concentrations of IL-1ra and IL-8, which showed different peaks during the course of treatment, reflected their different functions and patterns of secretion. Moreover the concentrations did not seem as sensitive as other inflammatory markers to evaluate disease activity during antituberculosis treatment. However, IL-1ra can be considered a marker for disease activity and response to treatment.
Adult
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Aged
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Aged, 80 and over
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Antitubercular Agents/therapeutic use
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Biological Markers/*blood
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C-Reactive Protein/analysis
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Comparative Study
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Female
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Human
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Interleukin-8/*blood
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Male
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Middle Aged
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Receptors, Interleukin-1/*antagonists & inhibitors
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Sialoglycoproteins/*blood
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Tuberculosis, Pulmonary/*blood/*drug therapy
6.Effect of cetirizine hydrochloride on the expression of substance P receptor and cytokines production in human epidermal keratinocytes and dermal fibroblasts.
Ji-Yong LIU ; Yong-Zhe ZHAO ; Cheng PENG ; Feng-Qian LI ; Quan-Gang ZHU ; Jin-Hong HU
Acta Pharmaceutica Sinica 2008;43(4):383-387
To investigate the effect of cetirizine hydrochloride on the expression of neurokinin 1 receptor (NK-1R) and cytokines production induced by substance P (SP) in HaCaT cells (a human epidermal keratinocyte cell line) and dermal fibroblasts. The effect of cetirizine on the expression of NK-1R protein was detected by flow cytometry and Western blotting analysis. The modulation of cetirizine on the production of interferon (IFN)-gamma, interleukin (IL)-1beta, IL-6 and IL-8 in HaCaT cells and fibroblasts was measured by ELISA. The results showed that cetirizine significantly inhibited the expression of NK-1R in HaCaT cells and fibroblasts. SP induced the production of IFN-gamma, IL-1beta and IL-8 in both cell types. Cetirizine 1-100 micromol x L(-1) inhibited SP-induced IL-1beta and IL-8 production in HaCaT cells and fibroblasts, while had no effect on the production of IFN-gamma in both cells. Both SP and cetirizine had no effect on the secretion of IL-6 in HaCaT cells and fibroblasts. These findings suggest that cetirizine may be involved in the treatment of SP-induced skin inflammation by inhibiting the expression of substance P receptor and regulation the production of IL-1beta and IL-8 in epidermal keratinocyte and dermal fibroblasts.
Anti-Allergic Agents
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pharmacology
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Cell Line
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Cetirizine
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pharmacology
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Fibroblasts
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cytology
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metabolism
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Histamine H1 Antagonists, Non-Sedating
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pharmacology
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Humans
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Interferon-gamma
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metabolism
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Interleukin-1beta
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metabolism
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Interleukin-8
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metabolism
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Keratinocytes
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cytology
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metabolism
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Receptors, Neurokinin-1
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metabolism
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Substance P
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pharmacology
7.Effects of interleukin-1 receptor antagonist on the apoptosis of eosinophil in guinea pig with asthma.
Acta Pharmaceutica Sinica 2003;38(9):661-664
AIMTo evaluate the effect of interleukin-1 receptor antagonist(IL-1ra) on apoptosis and associated mechanism of eosinophil in guinea pig with asthma.
METHODSA model of guinea pig with asthma was established. After inhalation of different concentrations of IL-1ra, asthma was induced in the guinea pig for 8 days, the concentration of eosinophil cationic protein (ECP) in serum and bronchoalveolar lavage fluid (BALF), IL-5 in serum, the eosinophil counts and apoptosis were assayed by radioimmunology, enzyme-linked immunosorbent assay(ELISA), fluoromicroscope and light microscope.
RESULTSIL-1ra indirectly decreased the level of IL-5 in serum, improved the apoptosis of eosinophil(EOS) in lung, then decreased the level of ECP in serum and BALF.
CONCLUSIONInhalation of nebulized IL-1ra showed protective effect against asthma through change of the activity and infiltration of EOS in lung.
Animals ; Apoptosis ; Asthma ; blood ; chemically induced ; pathology ; Blood Proteins ; metabolism ; Bronchoalveolar Lavage Fluid ; chemistry ; Eosinophil Granule Proteins ; Eosinophils ; drug effects ; pathology ; Female ; Guinea Pigs ; Interleukin 1 Receptor Antagonist Protein ; Interleukin-5 ; blood ; Leukocyte Count ; Male ; Ovalbumin ; Random Allocation ; Receptors, Interleukin-1 ; antagonists & inhibitors ; Ribonucleases ; blood ; metabolism ; Sialoglycoproteins ; pharmacology
8.Effects of TNF-alpha receptor blocking peptide on adjuvant arthritis in rats.
Ya-ping HE ; Zhuo-ya LI ; Xiao-dan JIANG ; Wei FENG ; Yong XU ; Ping XIONG
Acta Pharmaceutica Sinica 2003;38(12):889-892
AIMTo study the effects of TNF receptor blocking peptide on adjuvant arthritis in rats.
METHODSThe model of rat adjuvant arthritis was induced by injection of complete Freund's adjuvant. The TNF receptor blocking peptide was injected locally in the ankle. The ankle swelling, the pathologic changes in the ankle joint and the expression of IL-1 beta mRNA and TNF-alpha mRNA by peritoneal macrophages (RT-PCR) were observed.
RESULTSThe model of rat adjuvant arthritis induced by injection of complete Freund's adjuvant was similar to human rheumatoid arthritis. The treatment with TNF receptor blocking peptide for 10 days resulted in complete inhibition of joint swelling, a decrease in infiltration of inflammatory cell into joint tissue, an obvious alleviation of inflammatory pathological damages and an apparent decline of TNF-alpha mRNA and IL-1 beta mRNA of peritoneal macrophages of rats.
CONCLUSIONThe TNF receptor blocking peptide can protect the joint from inflammatory damage induced by adjuvant arthritis by suppression of TNF-alpha and IL-1 production, thereby alleviating the pathological injury of joint and controlling effectively the clinic course of arthritis.
Animals ; Ankle Joint ; pathology ; Arthritis, Experimental ; immunology ; pathology ; Interleukin-1 ; biosynthesis ; genetics ; Macrophages, Peritoneal ; metabolism ; Male ; Peptides ; pharmacology ; RNA, Messenger ; genetics ; Rats ; Rats, Wistar ; Receptors, Tumor Necrosis Factor ; antagonists & inhibitors ; Tumor Necrosis Factor-alpha ; biosynthesis ; genetics
9.A therapeutic anti-CD4 monoclonal antibody inhibits T cell receptor signal transduction in mouse autoimmune cardiomyopathy.
Zhao-hui WANG ; Yu-hua LIAO ; Jing YUAN ; Li ZHANG ; Min WANG ; Jing-hui ZHANG ; Zhong-ping LIU ; Ji-hua DONG
Chinese Medical Journal 2007;120(15):1319-1325
BACKGROUNDT cell immune abnormalities in patients with dilated cardiomyopathy (DCM) has been intensively studied over the past 10 years. Our previous study has suggested that immunization of mice with the peptides derived from human adenine nucleotide translocator (ANT) result in the production of autoantibodies against the ANT and histopathological changes similar to those in human DCM. The ANT peptides can induce autoimmune cardiomyopathy like DCM in Balb/c mice. In this study we aimed to focus on the molecular mechanism of T cells in the autoimmune cardiomyopathy mouse model by detecting the expression of the two T cell signaling molecules.
METHODSThe ANT peptides were used to cause autoimmune cardiomyopathy in Balb/c mice. Anti-L3T4 or rat anti-mouse IgG was administered to the mice (n = 6 in each group) simultaneously immunized with ANT. ELISA analysis was used to detect autoantibodies against the ANT peptides and the percentages of interferon-gamma and interleukin-4 producing cells among splenic CD4(+) lymphocytes was determined by using flow cytometry analysis. The expression of CD45 in spleen T cells was determined by immunohistochemistry and the mRNAs of T cell signaling molecules were detected by real-time PCR.
RESULTSTreatment of ANT immunized Balb/c mice with anti-CD4 mAb caused a reduction in the gene expression of P56lck and Zap-70 and a lower level of CD45 expression by spleen T cells. Also, a reverse of the Th1/Th2 ratio that results in the reduced production of antibodies against ANT was found in the anti-CD4 monoclonal antibodies (mAb) group. Whereas irrelevant antibody (rat anti-mouse IgG) did not suppress T cell signaling molecules nor inhibit CD45 expression, and control-antibody mice did not show any significant differences compared with the DCM group.
CONCLUSIONThe results show that anti-CD4 mAb is a powerful inhibitor of the early initiating events of T cell receptor (TCR) signal transduction in mouse autoimmune dilated cardiomyopathy.
Adenine Nucleotide Translocator 1 ; immunology ; Animals ; Antibodies, Monoclonal ; therapeutic use ; Autoantibodies ; blood ; Autoimmune Diseases ; therapy ; CD4 Antigens ; immunology ; Cardiomyopathy, Dilated ; immunology ; therapy ; Interferon-gamma ; biosynthesis ; Interleukin-4 ; biosynthesis ; Leukocyte Common Antigens ; analysis ; Mice ; Mice, Inbred BALB C ; Receptors, Antigen, T-Cell ; antagonists & inhibitors ; physiology ; Signal Transduction
10.Chronic treatment of enbrel in rats with isoproterenol-induced congestive heart failure limits left ventricular dysfunction and remodeling.
Weimin LI ; Runtao GAN ; Guifang SUN
Chinese Medical Journal 2002;115(8):1166-1169
OBJECTIVETo investigate the effect of chronic treatment of enbrel (EB), a TNF-alpha antagonist, in a well defined congestive heart failure (CHF) rat model and test the hypothesis that chronic treatment of EB in CHF rats may limit the progression of Left ventricular (LV) dysfunction and structure remodeling and decrease cardiac IL-1beta levels.
METHODSWe measured cardiac conformation, contractile performance and cytokines level in 8 age-matched normal adult rats (control group) and 8 rats with isoproterenol (ISO)-induced Heart failure (ISO group) and 8 rats with ISO-induced lesion but received EB treatment (EB group).
RESULTSLV end diastolic diameter and LV end systolic diameter in EB group were significantly less and LV fractional shortening was significantly larger than ISO group (9.2 +/- 0.3 mm vs 9.5 +/- 0.2 mm, 5.8 +/- 0.5 mm vs 6.5 +/- 0.3 mm, 0.37 +/- 0.03 vs 0.31 +/- 0.02, P < 0.05, P < 0.01, P < 0.01 respectively , but there was no significant difference of LV posterior wall thickness at end diastole between the two groups; LV end systolic pressure (P(ES)) dp/dt(max) in EB group were significantly greater than ISO group (104.8 +/- 4.6 mm Hg vs 98.4 +/- 4.9 mm Hg, 8395 +/- 940 mm Hg/s vs 6898 +/- 612 mm Hg, P < 0.05 P < 0.01 respectively), and LV end diastolic pressure (P(ED)) dp/dt(min), time constant of LV relaxation were significantly lower than ISO group (3.8 +/- 0.6 mm Hg vs 7.1 +/- 0.8 mm Hg, -5963 +/- 475 mm Hg/s vs-5030 +/- 316 mm Hg/s,15.4 +/- 0.8 ms vs 21.3 +/- 1.4 ms, P < 0.01, respectively . Although cardiac contractile performance in the EB group was greatly improved, there still was a big gap when compared with the control group. The ratio of LV weight to body weight in the EB group was significantly higher than control group 2.82 +/- 0.07 mg/g vs 2.28 +/- 0.08 mg/g, P < 0.01 but there was no significant difference when compared with the ISO group. There was no significant difference between the serum level of TNF-alpha in EB group and ISO group the it could not be detected in control group. TNF-alpha levels in LV of EB group was significantly higher than control group, 757.6 +/- 46.8 pg/g vs 367.5 +/- 22.7 pg/g, P < 0.01 but there was no significant difference when compared with ISO group. The IL-1beta level in LV of EB group was significantly lower than ISO group 356.2 +/- 28.5 pg/g vs 518.4 +/- 32.5 pg/g, P < 0.05 and it could not be detected in control group. The serum level of IL-1beta could not be detected in any rats.
CONCLUSIONEB administered as soon as possible when ISO induced myocardial necrosis occurs can greatly improve cardiac contraction, and the improvement may be partly due to a decrease in the IL-1beta level in LV, besides the direct blocking effect of EB on TNF-alpha. EB can alleviate cardiac remodeling by its effect on LVEDD.
Animals ; Body Weight ; drug effects ; Echocardiography ; Etanercept ; Heart Failure ; diagnostic imaging ; drug therapy ; physiopathology ; Immunoglobulin G ; therapeutic use ; Interleukin-1 ; analysis ; Isoproterenol ; pharmacology ; Male ; Rats ; Rats, Wistar ; Receptors, Tumor Necrosis Factor ; therapeutic use ; Tumor Necrosis Factor-alpha ; analysis ; antagonists & inhibitors ; Ventricular Dysfunction, Left ; prevention & control