Interleukin-1 Receptor Antagonist In Patients Research Articles

Inhibition of IL-1 Ameliorates Cardiac Dysfunction and Arrhythmias in a Murine Model of Kawasaki Disease.

Kawasaki disease (KD) is an acute febrile illness and systemic vasculitis often associated with cardiac sequelae, including arrhythmias. Abundant evidence indicates a central role for IL (interleukin)-1 and TNFα (tumor necrosis factor-alpha) signaling in the formation of arterial lesions in KD. We aimed to investigate the mechanisms underlying the development of electrophysiological abnormalities in a murine model of KD vasculitis. Lactobacillus casei cell wall extract-induced KD vasculitis model was used to investigate the therapeutic efficacy of clinically relevant IL-1Ra (IL-1 receptor antagonist) and TNFα neutralization. Echocardiography, in vivo electrophysiology, whole-heart optical mapping, and imaging were performed. KD vasculitis was associated with impaired ejection fraction, increased ventricular tachycardia, prolonged repolarization, and slowed conduction velocity. Since our transcriptomic analysis of human patients showed elevated levels of both IL-1β and TNFα, we asked whether either cytokine was linked to the development of myocardial dysfunction. Remarkably, only inhibition of IL-1 signaling by IL-1Ra but not TNFα neutralization was able to prevent changes in ejection fraction and arrhythmias, whereas both IL-1Ra and TNFα neutralization significantly improved vasculitis and heart vessel inflammation. The treatment of L casei cell wall extract-injected mice with IL-1Ra also restored conduction velocity and improved the organization of Cx43 (connexin 43) at the intercalated disk. In contrast, in mice with gain of function of the IL-1 signaling pathway, L casei cell wall extract induced spontaneous ventricular tachycardia and premature deaths. Our results characterize the electrophysiological abnormalities associated with L casei cell wall extract-induced KD and show that IL-1Ra is more effective in preventing KD-induced myocardial dysfunction and arrhythmias than anti-TNFα therapy. These findings support the advancement of clinical trials using IL-1Ra in patients with KD.

Prognostic impact of Interleukin-1 receptor antagonist in patients with documented coronary artery disease

BackgroundIL-1β-mediated inflammation contributes to development and progression of coronary artery disease (CAD). We aimed to assess the prognostic impact of the inflammatory marker Interleukin-1 receptor antagonist (IL1-Ra), reflecting high IL-1β activity, in patients with documented CAD. MethodsIL-1Ra levels were determined in 1337 subjects of the AtheroGene study, a prospective cardiovascular registry comprising patients with CAD as detected by coronary angiography presenting with acute coronary syndrome (ACS) or stable angina. Median follow-up was 6.4 years. ResultsPatients with IL1-Ra levels in the highest tertile presented more often with ACS (55% vs. 40% vs. 34%, p < 0.001), were more commonly treated with PCI (47% vs. 39% vs. 34%, p < 0.001), had lower left ventricular ejection fraction (LVEF) (61 ± 15% vs. 62 ± 15% vs. 65 ± 14%, p = 0.001) and higher hs-CRP levels (10.0 vs. 4.2 vs. 2.5 mg/L, p < 0.001). IL1-Ra levels at baseline were predictive for all-cause mortality in the total study cohort after adjustment for conventional cardiovascular risk factors, LVEF, hs-CRP and Troponin T (adjusted HR 1.45 (95% CI 1.16–1.82), p < 0.001). In a subgroup of patients with ACS, but not in those with stable angina, IL1-Ra was an independent predictor for cardiovascular mortality (ACS: adjusted HR 1.85 (95% CI 1.33–2.58), p < 0.001; stable angina: adjusted HR: 1.25 (95% CI 0.95–1.65), p = 0.11). ConclusionIL1-Ra is an independent predictor for adverse outcome in patients with documented CAD, beyond the prognostic value of hs-CRP and Troponin T in particular in the setting of ACS. For CAD patients our finding might improve both, risk assessment in secondary prevention and patient selection for anti-inflammatory treatment.

Inflammatory evidence for the psychosis continuum model

BackgroundInflammation and immune activation have been implicated in the pathophysiology of severe mental disorders. Previous studies of inflammatory markers, however, have been limited with somewhat inconsistent results. AimsWe aimed to determine the effect sizes of inflammatory marker alterations across diagnostic groups of the psychosis continuum and investigate association to antipsychotic medications. MethodsPlasma levels of soluble tumor necrosis factor receptor 1 (sTNF-R1), interleukin 1 receptor antagonist (IL-1Ra), osteoprotegerin (OPG), and von Willebrand factor (vWf) were measured in patients (n=992) with schizophrenia spectrum (SCZ, n=584), schizoaffective disorder (SA, n=93), affective spectrum disorders (AFF, n=315), and healthy controls (HC, n=638). ResultsLevels of sTNF-R1 (p=1.8×10−8, d=0.23) and IL-1Ra (p=0.002, d=0.16) were increased in patients compared to HC. The SCZ group had higher levels of sTNF-R1 (p=8.5×10−8, d=0.27) and IL-1Ra (p=5.9×10−5, d=0.25) compared to HC, and for sTNF-R1 this was also seen in the SA group (p=0.01, d=0.3) and in the AFF group (p=0.002, d=0.12). Further, IL-1Ra (p=0.004, d=0.25) and vWf (p=0.02, d=0.21) were increased in the SCZ compared to the AFF group. There was no significant association between inflammatory markers and use of antipsychotic medication. ConclusionWe demonstrate a small increase in sTNF-R1 and IL-1Ra in patients with severe mental disorders supporting a role of inflammatory mechanisms in disease pathophysiology. The increase was more pronounced in SCZ compared to AFF supporting a continuum psychosis model related to immune factors.

Markedly elevated plasma levels of interleukin-1 receptor antagonist in patients with dual diagnosis of schizophrenia and substance use disorders

Markedly elevated plasma levels of interleukin-1 receptor antagonist in patients with dual diagnosis of schizophrenia and substance use disorders

Effects of Occlusion on the Skin of Atopic Dermatitis Patients

Atopic dermatitis (AD) may be exacerbated by occlusion from items such as occlusive gloves or textiles, especially if the occlusion is removed suddenly, creating a steep humidity gradient. Most previous studies of occlusion have focused on normal skin. Occlusion has been shown to be beneficial in psoriatic skin, but many atopic patients complain of increased inflammation after occlusion. To evaluate the response of noninflamed AD skin to occlusion. Six patients with AD were patch-tested with occlusive polyethylene wrap and sodium lauryl sulfate (SLS) in standard Finn Chambers taped to noninflamed skin of the back. Cytokine and chemokine messenger ribonucleic acid (mRNA) for interleukin-8 (IL-8), interleukin-1 alpha (IL-1α), and interleukin-1 receptor antagonist (IL-1RA), as well as the 18S rRNA housekeeping gene, was obtained via tape-stripping the skin and measured using quantitative real-time polymerase chain reaction. We also measured transepidermal water loss after removal of occlusion. Polyethylene occlusion alone with abrupt removal induced IL-8 and IL-1α levels similar to or exceeding that of SLS. IL-1RA was up-regulated by SLS and occlusion, with SLS showing a stronger response. Removal of occlusion with polyethylene film up-regulates the inflammatory cytokines IL-8, IL-1α, and IL-1RA in patients with AD. This may explain the worsening of AD with the use of occlusive gloves, athletic equipment, and fabrics.

Measurement of interleukin-1 receptor antagonist in patients with systemic lupus erythematosus could predict renal manifestation of the disease

Interleukin-1 receptor antagonist (IL-1Ra) is a good indicator of disease activity in patients with systemic lupus erythematosus (SLE). Glucocorticosteroids are the most frequently used drugs in SLE. Our goal was to compare IL-1Ra activity in SLE patients with and without renal involvement and to determine the effect of different dosage of glucocorticosteroids used in 17 patients with active SLE without nephritis, 7 patients with inactive lupus nephritis (LN), and 8 patients with active LN, along with 10 healthy controls. IL-1Ra levels were measured in the serum of SLE patients by Human Luminex [100] analyzer. Both in patients with active SLE without nephritis and in patients with LN, serum levels of IL-1Ra ( p<0.001) were significantly higher compared with those in the controls. IL-1Ra was significantly higher in patients with active LN than in patients with inactive LN ( p = 0.028). The use of methylprednisolone was significantly higher in the active LN group compared with the inactive LN group ( p = 0.013). SLE patients with higher IL-1Ra are at lower risk for developing nephritis. The higher doses of glucocorticosteroids needed in active LN could be due to steroid resistance and IL-1Ra polymorphism. Measurement of IL-1Ra levels in SLE patients could help to predict future renal involvement.

Inflammation and Cardiovascular Disease

Inflammation plays an important role in the development and progression of a variety of cardiovascular conditions, most notably coronary atherosclerosis and congestive heart failure.1,2 A number of inflammatory molecules have been implicated in these processes, including interleukin-1 (IL-1). The IL-1 gene family consists of 3 proteins, IL-1α, IL-1β, and IL-1 receptor antagonist (IL-1ra). IL-1α and IL-1β exert their similar effects by binding to the IL-1 type I receptor. The IL-1 type II receptor also binds IL-1α and IL-1β but acts as a decoy receptor and is not involved in signal transduction, thereby counterbalancing the inflammatory effects of IL-1α and IL-1β. IL-1ra is an endogenous inhibitor of IL-1α and IL-1β, which competitively binds to the IL-1 type I receptor without activating it.3 Article p 2662 Both IL-1 and IL-1ra are produced by endothelial cells, smooth muscle cells, and macrophages. IL-1 secretion is induced by microbial products that stimulate toll-like receptors and by certain endogenous triggers, such as uric acid produced during cell death. Both types of agonists stimulate a cytosolic complex of proteins termed the inflammasome, which activates caspase-1 to enable secretion of IL-1β. The potential of this IL-1β pathway for systemic inflammation is demonstrated not only by gout but also by the clinical effects of activating mutations in cryopyrin (also known as NALP3 or CIAS1), one of the inflammasome components, which causes familial cold autoinflammatory syndrome, Muckle-Wells syndrome, and neonatal-onset multisystem inflammatory disease.4 Circulating levels of IL-1 are associated with the presence of traditional cardiac risk factors, such as diabetes mellitus, hypertension, smoking, and dyslipidemia. Elevated levels of IL-1 result in secretion of chemokines and other cytokines (eg, IL-6), increased expression of adhesion molecules, activation of endothelial and smooth muscle cell proliferation, macrophage activation, and increased vascular permeability. This cascade promotes atherosclerosis and plaque destabilization. IL-1 and …

Decreased levels of peritoneal interleukin-1 receptor antagonist in patients with endometriosis and disease-related dysmenorrhea

To determine the level of interleukin-1 receptor antagonist (IL-1ra) in peritoneal fluid (PF) and serum in patients with endometriosis. A prospective analytical study. University-affiliated obstetrics and gynecology academic training hospital. One hundred eighteen patients underwent laparoscopy for benign gynecologic diseases. Peripheral blood and PF were obtained before and during surgical procedures, and the levels of IL-1ra were measured. The concentrations of IL-1ra in PF and serum were correlated with the presence of endometriosis, disease stage, and the phase of menstrual cycle. Peritoneal fluid IL-1ra concentrations were significantly lower in patients with endometriosis than in patients without endometriosis. Peritoneal fluid IL-1ra concentrations decreased with the increased severity of endometriosis and also decreased in disease-related dysmenorrhea; serum IL-1ra levels showed no significant difference between the patients with and without endometriosis. The concentrations of IL-1ra in PF and serum were not correlated with the phase of menstrual cycle. Our results suggested that decreased levels of PF IL-1ra in patients with endometriosis and disease-related dysmenorrhea may play an important role in the pathogenesis of this disease.

A novel CIAS1mutation in a Japanese patient with chronic infantile neurological cutaneous and articular syndrome

We report here a Japanese patient with chronic infantile neurological cutaneous and articular (CINCA) syndrome with a novel mutation in the CIAS1gene. An 18-month-old girl was referred to our hospital for the evaluation of skin manifestations. She was born at 36 weeks of gestation with a birth weight of 1584 g. Shortly after birth, she had generalised maculopapular erythema, an increased WBC count, and an increased serum C-reactive protein level. On admission, her weight, height, and head circumstance were 8150 g (-1.6 SD), 72 cm (-2.6 SD), and 49.5 cm (+2.3 SD), respectively. The physical examination revealed maculopapular erythema on her trunk (Fig. 1A) and extremities, a wide fontanelle (4·5 cm), frontal bossing, and a saddle nose. Her joints were normal. Haematological investigations revealed the following: a WBC count of 22.01·10/l (48.5% neutrophils, 42.5% lymphocytes, 0.5% monocytes, 7.5% eosinophils and 1.0% atypical lymphocytes), a haemoglobin of 8.0 g/dl, and a platelet count of 590·10/l. The ESR was 91 mm/h. Serum IL-1b and IL-6 concentrations were 7.51 pg/ml (less than 5.0 pg/ml in normal controls) and less than 5.0 pg/ml (less than 5.0 pg/ml in normal controls), respectively. The CSF examination showed a pleocytosis (156 cells/ll, 59.4% neutrophils, and 40.6% mononuclear cells), a protein concentration of 110 mg/ dl, and a glucose concentration of 27 mg/dl. IL-1b and IL-6 concentrations were less than 5.0 pg/ml (less than 5.0 pg/ml in normal controls) and 312 pg/ml (less than 5.0 pg/ml in normal controls), respectively. The ophthalmological examination revealed bilateral papilloedema. A skin biopsy was performed and an infiltration of inflammatory cells, predominantly polymorphonuclear cells, was observed in the upper dermis and perivascular area (Fig. 1B). As shown in Fig. 1C, a heterozygous mutation (c.1431C>A, N477K) was observed within the NACHT (NAIP, CIITA, HET-E, and TP-1) domain in exon 3 of the CIAS1gene, which has not been previously reported. The mutation was not observed in both parents (Fig. 1C). Moreover, this mutation was not observed among 100 healthy Japanese donors by using allelespecific PCR (data not shown). Mutations in the CIAS1gene were recently found to be associated with a spectrum of auto-inflammatory disorders that include CINCA syndrome, Muckle-Wells syndrome, and familial cold urticaria [1,3]. The CIAS1gene product, cryopyrin, has been implicated in the regulation of inflammation [5]. Previous reports indicated that 6 among 13 CINCA patients had CIAS1mutations [1], and almost all the CIAS1mutations were identified in exon 3 that encodes the NACHT domain [2,6]. The mutation found in this patient was within the NACHT domain but not in the hotspots [6]. Since the NACHT domain plays a crucial role in protein oligomerisation, the mutant cryopyrin may have an increased propensity to oligomerize spontaneously, which leads to the binding to the apoptosis-associated specklike protein containing a card, inflammasome formation, activation of caspase-1, and over-secretion of IL-1b [5]. The effectiveness of IL-1 receptor antagonist in patients with CINCA syndrome strongly suggests the central role of IL-1b in this disorder [4]. IL-1 receptor antagonist will be given to this patient. H. Takada (&) AE K. Kusuhara AE A. Nomura AE S. Ohga AE T. Hara Department of Paediatrics, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, 812-8582 Fukuoka, Japan E-mail: takadah@pediatr.med.kyushu-u.ac.jp Tel.: +81-92-6425421 Fax: +81-92-6425435

Circulating levels of proinflammatory cytokines and neutrophil-platelet aggregates in patients with coronary artery disease

Several lines of evidence indicate that increased inflammatory activity in peripheral blood is associated with the acute coronary syndrome. Systemic inflammation in clinically stable conditions of coronary artery disease has been less studied. We examined cytokine profiles in 20 patients who had acute coronary syndrome, 45 who had angiographically verified coronary artery disease and stable angina pectoris, and 45 healthy controls. Circulating levels of C-reactive protein, interleukin-1 receptor antagonist, interleukin-2 receptor, interleukin-6, interleukin-10, and interleukin-18 were determined. Subpopulations of peripheral immune cells, including neutrophil-platelet aggregates, were analyzed by 3-color flow cytometry using a panel of monoclonal antibodies. Patients who had acute coronary syndrome and stable angina pectoris had significantly higher levels of C-reactive protein, interleukin-6, and interleukin-1 receptor antagonist than did controls, whereas levels of interleukin-2 receptor, interleukin-10, and interleukin-18 were similar across groups. Patients had significantly more neutrophils, and the numbers of neutrophil-platelet aggregates were particularly large in patients who had stable angina pectoris. High levels of C-reactive protein, interleukin-6, and interleukin-1 receptor antagonist in patients were significantly related to numbers of neutrophils and neutrophil-platelet aggregates but not to other immune cell subpopulations. The data suggest that the interaction between neutrophils and platelets is an important component of proinflammatory activity seen in peripheral blood of stable and unstable forms of coronary artery disease.

Clinical significance of interleukin-1 receptor antagonist in patients with cervical carcinoma

Objective Our purpose was to determine the clinical significance of interleukin-1 receptor antagonist (IL-1ra), which is an endogenous inhibitor cytokine of IL-1, in patients with cervical carcinoma. Methods Tissue IL-1ra expression and serum IL-1ra level were examined by enzyme-linked immunosorbent assay (ELISA), Western blotting, and immunohistochemistry in normal controls and patients with cervical carcinoma. Results Tissue IL-1ra protein level by ELISA was significantly higher in squamous cell carcinoma ( n = 9) than in the normal cervix ( n = 7) and adenocarcinoma ( n = 3). Western blotting confirmed the main presence of intracellular IL-1ra type 1 in squamous cell carcinoma. Immunohistochemistry demonstrated significant IL-1ra expression only in tumor cells of squamous cell carcinoma. Elevation of serum IL-1ra level was found in patients with squamous cell carcinoma ( n = 38) compared to normal women ( n = 13), but not in patients with adenocarcinoma ( n = 9). Although serum IL-1ra level did not correlate with clinical stage or any other tumor marker, high serum IL-1ra level was associated with pelvic lymph node metastasis and poor prognosis in patients with squamous cell carcinoma. On the other hand, these results were not obtained in patients with cervical adenocarcinoma. Conclusion IL-1ra may play important roles in local and general malignant behaviors in patients with cervical squamous cell carcinoma, and measurement of serum IL-1ra level may be useful in predicting patient survival.

Helping to understand studies examining genetic susceptibility to sepsis

Helping to understand studies examining genetic susceptibility to sepsis

Prognostic value of interleukin-1 receptor antagonist in patients undergoing percutaneous coronary intervention

Elevated plasma levels of inflammatory markers, such as C-reactive protein (CRP), have been associated with adverse outcome in selected patients with coronary artery disease (CAD) treated with coronary angioplasty or stenting. The aim of this study was to evaluate the predictive value of preprocedural interleukin-1 receptor antagonist (IL-1Ra) plasma levels for long-term major adverse cardiac events (MACE) in a series of unselected patients with symptomatic CAD treated with percutaneous coronary intervention (PCI). Seventy-three consecutive patients (62 men, aged 62 ± 9 years) undergoing PCI were enrolled in a prospective follow-up study. IL-1Ra and CRP plasma levels were measured before the procedure; 36 patients (49%) had unstable angina pectoris on admission, 37 (51%) had chronic stable angina pectoris, and 30 (41%) had multivessel CAD, 15 of whom underwent multivessel PCI. Success was achieved in all 73 patients, with coronary stenting performed in 63 (86%). Follow-up clinical assessment included occurrence of MACE at 3, 6, 12, and 18 months. Logistic regression analysis, performed to determine independent predictors of MACE, identified IL-1Ra levels in the upper quartile as the only independent predictive factor of MACE at 18 months (19% in the fourth quartile vs 0% in the first quartile; p = 0.032). Patients with high preprocedural CRP levels (fourth quartile) had a nonsignificant increased risk of MACE (p = 0.09). Thus, preprocedural IL-1Ra plasma levels appear to be a valuable independent predictive factor of MACE in unselected patients undergoing PCI.

Correlation of metalloproteinase-2 and -9 with proinflammatory cytokines interleukin-1�, interleukin-12 and the interleukin-1 receptor antagonist in patients with chronic uveitis

Correlation of metalloproteinase-2 and -9 with proinflammatory cytokines interleukin-1�, interleukin-12 and the interleukin-1 receptor antagonist in patients with chronic uveitis

Correlation of metalloproteinase-2 and -9 with proinflammatory cytokines interleukin-1ß, interleukin-12 and the interleukin-1 receptor antagonist in patients with chronic uveitis

Purpose. Matrix metalloproteinases have been shown to play a role in active uveitis. Transcription of MMPs is induced by a number of growth factors and cytokines. This study investigates the role of MMPs in chronic uveitis and correlates the amounts of MMP-2 and -9 in intraocular samples to the intraocular levels of proinflammatory cytokines (Interleukin-1 [IL-1], Interleukin-12 [IL-12] and Interleukin-1 receptor antagonist [IL-1ra]). Methods. Aqueous humor of 16 patients was collected during surgical or diagnostic procedures (control group: cataract patients). MMP-2 and -9 were measured using zymography. IL-1ß, IL-12 and IL-1ra were evaluated by ELISA. Results. We found MMP-2 and -9 in all of our uveitis patients. In the control group only MMP-2 was seen. Higher levels of MMP-2 and -9 were found in patients with higher activity of uveitis (p < 0.014 for MMP-2, p < 0.0054 for MMP-9). The amounts of IL-1ß, IL-12 and IL-1ra detected in our uveitis patients correlated with levels of MMP-2 (p < 0.07, p < 0.0004, p < 0.03) and MMP-9 (p < 0.003, p < 0.0001, p < 0.002), and IL-12 (p < 0.004, p < 0.0001). Patients with moderately active uveitis presented with twice the level of MMP-2 as the control group; MMP-9 levels reached up to 92% of the amounts found in patients with active uveitis. Two patients in remission for almost one year still had detectable intraocular MMP-9 levels. Conclusion. Our data suggests that the high levels of MMPs found in patients with chronic uveitis might contribute to the damage often seen in these eyes. Since MMPs are capable of releasing proinflammatory cytokines bound to components of the extracellular matrix, and facilitate the secretion of active TNF-a by cleavage of the membrane bound form, it is conceivable that MMPs contribute to the chronicity of some uveitis cases.

Clinical presentation of thyroid associated orbitopathy.

ThyroidVol. 8, No. 5 Clinical Presentation of Thyroid Associated OrbitopathyPAT KENDALL-TAYLOR and PETROS PERROSPAT KENDALL-TAYLORSearch for more papers by this author and PETROS PERROSSearch for more papers by this authorPublished Online:3 Feb 2009https://doi.org/10.1089/thy.1998.8.427AboutSectionsPDF/EPUB ToolsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail "Clinical Presentation of Thyroid Associated Orbitopathy." , 8(5), pp. 427–428FiguresReferencesRelatedDetailsCited ByMaladie de BasedowExtrathyroidal Manifestations of Thyroid DiseaseNeuroimaging Clinics of North America, Vol. 31, No. 3Recent advances in thyroid eye disease: An overview15 July 2021 | IP International Journal of Ocular Oncology and Oculoplasty, Vol. 7, No. 2Evaluating the Thyroid Eye Disease Patient23 March 2021 | International Ophthalmology Clinics, Vol. 61, No. 2The Role of Vitamin D Receptor Gene Polymorphisms in Thyroid-Associated Orbitopathy19 August 2019 | Ocular Immunology and Inflammation, Vol. 46Association of Risk of Obstructive Sleep Apnea With Thyroid Eye Disease: Compressive Optic NeuropathyOphthalmic Plastic & Reconstructive Surgery, Vol. 35, No. 3Thyroid Eye Disease28 April 2019Optical Coherence Tomography Thickness Measurements of the Extraocular Rectus Muscle Tendons in Graves' OphthalmopathyJournal of Pediatric Ophthalmology & Strabismus, Vol. 55, No. 6Response to tocilizumab treatment in Graves’ ophthalmopathy by measuring rectus muscle thickness and chemosis using optical coherence tomographyArchivos de la Sociedad Española de Oftalmología (English Edition), Vol. 93, No. 8Evaluación del grosor de los músculos extraoculares y la quemosis tras tocilizumab en oftalmopatía de Graves mediante tomografía de coherencia ópticaArchivos de la Sociedad Española de Oftalmología, Vol. 93, No. 8Grading Severity and Activity in Thyroid Eye DiseaseOphthalmic Plastic & Reconstructive Surgery, Vol. 34, No. 4SMedical and Surgical Options in Thyroid Eye Disease27 June 2018Raising awareness of Graves' orbitopathy with early warning cards4 September 2017 | Clinical Endocrinology, Vol. 87, No. 6An Animal Model of Graves’ Orbitopathy2 December 2015Recurrent Thyroid Eye DiseaseOphthalmic Plastic & Reconstructive Surgery, Vol. 31, No. 6Natural History of Thyroid Eye Disease24 October 2014Difficult-to-Treat HyperthyroidismAssessment and Management Plan for Graves’ OrbitopathyEvaluating Graves’ OrbitopathyBest Practice & Research Clinical Endocrinology & Metabolism, Vol. 26, No. 3Locally produced insulin-like growth factor-1 by orbital fibroblasts as implicative pathogenic factor rather than systemically circulated IGF-1 for patients with thyroid-associated ophthalmopathy9 December 2011 | Graefe's Archive for Clinical and Experimental Ophthalmology, Vol. 250, No. 3Evaluation of Hyperthyroidism and Hyperthyroid Goiter15 June 2012Maladie de BasedowThyroid orbitopathy possibly predisposes to late-onset of periocular lymphoma26 August 2005 | Eye, Vol. 20, No. 6Predictors of Disease Severity in Thyroid-Related Orbitopathy9 April 2013Evaluation of Extraocular Muscles in the Edematous Phase of Graves Ophthalmopathy on Contrast-Enhanced Fat-Suppressed Magnetic Resonance ImagingJournal of Computer Assisted Tomography, Vol. 28, No. 1La thyroïdectomie aggrave-t-elle l'ophtalmopathie basedowienne ?Annales de Chirurgie, Vol. 128, No. 2Epidemiology and Prevention of Graves' Ophthalmopathy9 July 2004 | Thyroid, Vol. 12, No. 10Serum Levels of Tumor Necrosis Factor-α, Soluble Intercellular Adhesion Molecule-1, Soluble Vascular Cell Adhesion Molecule-1, and Soluble Interleukin-1 Receptor Antagonist in Patients with Thyroid Eye Disease Undergoing Treatment with Somatostatin Analogues9 July 2004 | Thyroid, Vol. 11, No. 12Thyroid-associated orbitopathy developed during hormone replacement therapy20 December 2001 | Acta Ophthalmologica Scandinavica, Vol. 79, No. 4Clinical Presentation and Natural History of Graves’ OphthalmopathyIncreased Frequency of Euthyroid Ophthalmopathy in Patients with Graves' Disease Associated with Myasthenia Gravis30 January 2009 | Thyroid, Vol. 10, No. 9Management of Graves’ Ophthalmopathy: Reality and Perspectives*7 November 2016 | Endocrine Reviews, Vol. 21, No. 2Thyroid-Associated Ophthalmopathy: Clinical Features, Pathogenesis, and Management29 September 2008 | Critical Reviews in Clinical Laboratory Sciences, Vol. 37, No. 6Evaluation of Hyperthyroidism and Hyperthyroid Goiter Volume 8Issue 5May 1998 To cite this article:PAT KENDALL-TAYLOR and PETROS PERROS.Clinical Presentation of Thyroid Associated Orbitopathy.Thyroid.May 1998.427-428.http://doi.org/10.1089/thy.1998.8.427Published in Volume: 8 Issue 5: February 3, 2009PDF download

Dysregulation of the in vivo production of interleukin-1 receptor antagonist in patients with rheumatoid arthritis. Pathogenetic implications.

Patients with rheumatoid arthritis (RA) have defective hypothalamic responses to inflammation, possibly because of excessive production of cytokine inhibitor, which could blunt the effects of cytokines on the hypothalamus, or because of an imbalance between interleukin-1 beta (IL-1 beta) and interleukin-1 receptor antagonist (IL-1Ra), which could create a mainly proinflammatory state. The present study was undertaken to investigate these possibilities. The in vivo kinetics of IL-1 beta and IL-1Ra secretion were studied in patients with RA, osteoarthritis (OA), and chronic osteomyelitis (OM), and in normal controls before and after surgery. The 24-hour levels of IL-1Ra were significantly increased in RA (P < 0.001), but there was no diurnal variation in any group. Preoperative levels of IL-1Ra were higher in RA and OA sera (P = 0.001). After surgery, IL-1Ra behaved like an acute-phase reactant protein in all subjects. IL-1 beta was 10-20 times higher in RA than in OM and OA patients at baseline, but the percentage increase in all groups postoperatively was the same. RA patients had an IL-1Ra:IL-1 beta ratio of 26.2 +/- 3.7 (mean +/- SEM) at baseline (OM patients 89.2 +/- 5.8 and OA patients 1,310 +/- 363); this increased to 66.5 +/- 19.8 after surgery (OM patients 120 +/- 6.7 and OA patients 325.8 +/- 106). RA patients have a dysregulation of IL-1Ra production, and it seems unlikely that the defective hypothalamic response seen in RA is due to a functional deficit of IL-1 beta.

Classification of Eye Changes of Graves' Disease

Classification of Eye Changes of Graves' Disease