Circulating proinflammatory cytokines (IL-1β, TNF-α, and IL-6) and IL-1 receptor antagonist (IL-1Ra) in fulminant hepatic failure and acute hepatitis

Sekiyama, Kazuhiko; Yoshiba, Makoto; Thomson, Angus W.

doi:10.1111/j.1365-2249.1994.tb06609.x

Cited by 160 publications

(88 citation statements)

References 39 publications

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“…The balance between IL-1 and IL-1Ra seems crucial in inflammatory diseases [15][16][17][18]. Although IPF is not primarily an inflammatory disease, IPF is characterized by high levels of inflammatory parameters.…”

Section: Il-1 Receptor Antagonist In Ipfmentioning

confidence: 99%

Genetic variability in the IL1RN gene and the balance between interleukin (IL)-1 receptor agonist and IL-1β in idiopathic pulmonary fibrosis

Barlo¹,

Moorsel

Korthagen³

et al. 2011

Clinical and Experimental Immunology

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SummaryIdiopathic pulmonary fibrosis (IPF) is a rapidly progressive interstitial lung disease of unknown aetiology. Interleukin (IL)-1b plays an important role in inflammation and has been associated with fibrotic remodelling. We investigated the balance between IL-1b and IL-1 receptor antagonist (IL-1Ra) in bronchoalveolar lavage fluid (BALF) and serum as well as the influence of genetic variability in the IL1B and IL1RN gene on disease susceptibility and cytokine levels. In 77 IPF patients and 349 healthy controls, single nucleotide polymorphisms (SNPs) in the IL1RN and IL1B genes were determined. Serum and BALF IL-1Ra and IL-1b levels were measured using a multiplex suspension bead array system and were correlated with genotypes. Both in serum and BALF a significantly decreased IL-1Ra/IL-1b ratio was found in IPF patients compared to healthy controls. In the IL1RN gene, one SNP was associated with both the susceptibility to IPF and reduced IL-1Ra/IL-1b ratios in BALF. Our results show that genetic variability in the IL1RN gene may play a role in the pathogenesis of IPF and that this role may be more important than thought until recently. The imbalance between IL-1Ra and IL-1b might contribute to a proinflammatory and pro-fibrotic environment in their lungs.

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Section: Il-1 Receptor Antagonist In Ipfmentioning

confidence: 99%

Genetic variability in the IL1RN gene and the balance between interleukin (IL)-1 receptor agonist and IL-1β in idiopathic pulmonary fibrosis

Barlo¹,

Moorsel

Korthagen³

et al. 2011

Clinical and Experimental Immunology

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“…Values with a diagnostic accuracy greater than 50% had acceptable specificity but low sensitivity (Table 6). A threshold value of greater than 200 mol/L had specificity of 92% (95% CI: 88-95) but sensitivity of 25% (17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33), failing to identify 36 of 48 (75%) patients who developed ICH.…”

Section: Admissionmentioning

confidence: 99%

Arterial ammonia and clinical risk factors for encephalopathy and intracranial hypertension in acute liver failure

et al. 2007

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High circulating ammonia concentrations are common in patients with acute liver failure (ALF) and are associated with hepatic encephalopathy (HE) and intracranial hypertension (ICH). Other risk factors are poorly characterized. We evaluated the relation of the admission arterial ammonia concentration and other clinical variables with the development of HE and ICH. Arterial ammonia was measured on admission to the intensive care unit in 257 patients; 165 had ALF and severe HE, and there were 3 control groups: acute hepatic dysfunction without severe HE (n ‫؍‬ 50), chronic liver disease (n ‫؍‬ 33), and elective surgery (n ‫؍‬ 9). Variables associated with ICH and HE were investigated with regression analysis. Ammonia was higher in ALF patients than controls. An independent risk factor for the development of severe HE and ICH, a level greater than 100 mol/L predicted the onset of severe HE with 70% accuracy. The model for end-stage liver disease (MELD) score was also independently predictive of HE, and its combination with ammonia increased specificity and accuracy. ICH developed in 55% of ALF patients with a level greater than 200 mol/L, although this threshold failed to identify most cases. After admission, ammonia levels remained high in those developing ICH and fell in those who did not. Youth, a requirement for vasopressors, and renal replacement therapy were additional independent risk factors. Conclusion: Ammonia is an independent risk factor for the development of both HE and ICH. Additional MELD scoring improved the prediction of HE. T here is now strong evidence of a central role for ammonia in the pathogenesis of hepatic encephalopathy (HE) that defines acute liver failure (ALF) and the cerebral edema (CE) and intracranial hypertension (ICH) that contribute to the high mortality seen in this condition. Elevations in the circulating ammonia concentration are a frequent finding in experimental and human ALF and appear to be closely related to these complications. 1-3 Experimental studies have demonstrated ammonia-induced changes in neurotransmitter synthesis and release, neuronal oxidative stress, impaired mitochondrial function, and osmotic disturbances resulting from astrocytic metabolism of ammonia to glutamine. [4][5][6] The net result of these changes is a marked alteration in cerebral function and astrocytic swelling. [5][6][7] Recent studies reporting circulating ammonia concentrations in patients with ALF have found levels higher than those seen in patients with HE accompanying chronic liver disease (CLD). 2,3,8,9 The magnitude of the elevation of ammonia, particularly if it is above 150 mol/L, has been reported to be related to an increased risk of major cerebral complications, including reduced consciousness level, seizures, cerebral herniation (CH), and death. 2,3,8,10,11 If confirmed, these findings have the potential to alter clinical practice; patients identified as being at high risk for HE and ICH in this way could be targeted with specific therapies to reduce the circulating ammonia concen-

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“…[8] Extensive genetic polymorphisms have also been described, which in many cases appear to play an important part in their level of expression and have been linked to a variety of diseases, [6] as a variety of experiments has shown that either excessive or insufficient production of cytokines may contribute significantly to the pathophysiology of a range of diseases [2] including hepatic diseases. [9] GENERAL PROPERTIES OF CYTOKINES Cytokines can be produced by virtually every nucleated cell type in response to injurious stimuli [ Table 2]. [10] Mostly, cytokines are produced and act locally.…”

Section: Introductionmentioning

confidence: 99%

Physiological potential of cytokines and liver damages

Mannaa¹,

Abdel-Wahhab²

2016

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Cytokines are soluble extracellular small molecular weight protein or peptide. They are produced by virtually every nucleated cell type in response to injurious stimuli to control body metabolism, infection, inflammation and tissue or neuronal damage; therefore acting as messengers between tissues and the immune system; and participating in many physiological processes through their either anti-inflammatory or pro-inflammatory characteristics. Many cytokines have multiple cellular sources and targets, as well as many natural inducers and inhibitors. In pathophysiological conditions and during the early phase of chronic liver diseases, agent like virus, bacteria, parasites, ethanol, or toxins, induce secretion of cytokines at high levels. The presence of cytokine antagonists and soluble cytokine receptors, often released in concert with their respective cytokine agonist, presents additional complexity to interpretation.

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Circulating proinflammatory cytokines (IL-1β, TNF-α, and IL-6) and IL-1 receptor antagonist (IL-1Ra) in fulminant hepatic failure and acute hepatitis

Cited by 160 publications

References 39 publications

Genetic variability in the IL1RN gene and the balance between interleukin (IL)-1 receptor agonist and IL-1β in idiopathic pulmonary fibrosis

Genetic variability in the IL1RN gene and the balance between interleukin (IL)-1 receptor agonist and IL-1β in idiopathic pulmonary fibrosis

Arterial ammonia and clinical risk factors for encephalopathy and intracranial hypertension in acute liver failure

Physiological potential of cytokines and liver damages

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