Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P05231 (interleukin-6)
 23,907 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sepsis and septic shock are common problems in the ICU and carry a very high mortality. Myocardial depression is a common finding in patients with sepsis, and is usually reversible as the patient recovers. Both exogenous mediators, such as endotoxin, and endogenous cytokines, including tumor necrosis factor-alpha, interleukin-1beta, and interleukin-6, have been implicated as important factors in the pathophysiology of septic shock and the development of myocardial depression in sepsis. Nitric oxide has also been implicated in the pathophysiology of the cardiovascular response to sepsis. Better understanding of the roles and interactions of these substances will be necessary to develop more effective therapies without increasing morbidity and mortality.
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PMID:Pathophysiology of cardiovascular dysfunction in septic shock. 965 20

Activation and inhibition of coagulation and fibrinolysis was analyzed in bronchoalveolar lavage (BAL) fluids obtained from endotoxin-challenged chimpanzees. The mediatory role of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) on endotoxin-induced changes in bronchoalveolar coagulation and fibrinolysis was investigated in experiments in which the infusion of endotoxin was combined with the administration of monoclonal anti-TNF-alpha or anti-IL-6 antibodies. Endotoxin infusion elicited a marked increase in bronchoalveolar thrombin generation as measured by levels of prothrombin activation fragment F1+2 and thrombin-antithrombin complexes. Markers for intrinsic pathway activation were not detectable, suggesting that the thrombin generation was mediated by the tissue factor-dependent route. Levels of antithrombin were low before the injection of endotoxin and not detectable hereafter. The administration of anti-IL-6 antibody completely abolished the endotoxin-induced activation of bronchoalveolar coagulation, whereas treatment with anti-TNF-alpha antibody only partly inhibited this effect. Bronchoalveolar fibrinolytic activity, due to urokinase-type plasminogen activator (u-PA), was significantly depressed after endotoxin injection, mainly due to a striking increase in plasminogen activator inhibitor-2 levels in BAL fluid. The endotoxin-induced effects on bronchoalveolar fibrinolysis could be blocked by the simultaneous administration of anti- TNF-alpha antibodies. We conclude that endotoxemia results in the activation of bronchoalveolar coagulation, which is apparently mediated by the tissue factor route of coagulation activation and which may be amplified by consumption of antithrombin III. Bronchoalveolar fibrinolytic activity is significantly abolished by increased levels of mainly PAI-2 after the injection of endotoxin. The endotoxin-induced effects on bronchoalveolar coagulation appears to be mediated by IL-6, whereas TNF-alpha seems to be the pivotal mediator of the endotoxin-induced depression of bronchoalveolar fibrinolysis.
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PMID:Differential effects of anti-cytokine treatment on bronchoalveolar hemostasis in endotoxemic chimpanzees. 965 12

We evaluated the protective effect of interleukin-10 (IL-10) against murine gut-derived sepsis caused by Pseudomonas aeruginosa. Gut-derived sepsis was induced by administering cyclophosphamide and ampicillin while feeding P. aeruginosa to specific-pathogen-free mice. Treating mice with recombinant human IL-10 (rhIL-10) at 1.0 or 5.0 microg/mouse twice a day following the second cyclophosphamide administration significantly increased the survival rate compared to that of control mice treated with saline; however, treatment with rhIL-10 at 0.1 microg/mouse did not result in significant protection. Bacterial counts in the liver, spleen, and blood were all significantly lower in mice treated with rhIL-10 than in saline-treated control mice. Treatment with rhIL-10 significantly suppressed tumor necrosis factor alpha, interleukin-1beta, interleukin-6, and gamma interferon levels in the serum of mice following induction of gut-derived sepsis. We also studied the effect of IL-10 on leukocyte recovery after cyclophosphamide treatment of mice. Administration of rhIL-10 intraperitoneally at 1. 0 microg/mouse significantly accelerated the recovery of leukocytes in comparison with that of the group of saline-treated controls. These results indicate that IL-10 shows a protective effect against gut-derived P. aeruginosa sepsis. We suspect that the mechanism of this effect is that IL-10 regulates in vivo production of inflammatory cytokines. Furthermore, acceleration of leukocyte recovery by IL-10 after cyclophosphamide-induced depression may also play an important role in this protection.
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PMID:Effect of interleukin-10 on gut-derived sepsis caused by Pseudomonas aeruginosa in mice. 979 15

Fibromyalgia is a chronic, painful musculoskeletal disorder characterized by widespread pain, pressure hyperalgesia, morning stiffness and by an increased incidence of depressive symptoms. The etiology, however, has remained elusive. The aim of the present study was to examine the inflammatory response system (IRS) in fibromyalgia. Serum interleukin-6 (IL-6), soluble IL-6 receptor (sIL-6R), sgp130, sIL-1R antagonist (IL-1RA) and sCD8 were determined in 33 healthy volunteers and in 21 fibromyalgia patients, classified according to the American College of Rheumatology criteria. Severity of illness was measured with several pain scales, dolorimetry and the Hamilton Depression Rating Scale (HDRS). Serum sgp130 was significantly higher and serum sCD8 significantly lower in fibromyalgia patients than in healthy volunteers. Serum sIL-6R and sIL-1RA were significantly higher in fibromyalgia patients with an increased HDRS score (> or = 16) than in normal volunteers and fibromyalgia patients with a HDRS score < 16. In fibromyalgia patients, an important part of the variance in sCD8 (50.3%) and IL-1RA (19.3%) could be explained by the HDRS score; 74.3% of the variance in sIL-6R was explained by the combined effects of pain symptoms and the HDRS score; and 25.9% of the variance in serum sgp130 was explained by stiffness. The results support the contention that pain and stiffness in fibromyalgia may be accompanied by a suppression of some aspects of the IRS and that the presence of clinically significant depressive symptoms in fibromyalgia is associated with some signs of IRS activation.
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PMID:The immune-inflammatory pathophysiology of fibromyalgia: increased serum soluble gp130, the common signal transducer protein of various neurotrophic cytokines. 1034 65

Changes in the time courses of serum levels of interleukin-6 (IL6) and the soluble form of CD25 (sCD25) were evaluated in 48 burned patients (31 had sepsis, 21 died). Differences among groups along the time were assessed with ANOVA. The Pearson's r correlation coefficient was used to relate quantitative variables. ROC curves were constructed to analyse the prognostic value of IL6 and sCD25. The values of IL6 and sCD25 were related to treatment outcome and time post-burn. In general, two patterns emerged: In non-survivors, there was a depression of sCD25 with time, and an increase in IL6 levels previous to death, whereas survivors had the opposite pattern. On admission, patients with higher levels of sCD25 had a bad prognosis.
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PMID:Dynamic profiles of interleukin-6 and the soluble form of CD25 in burned patients. 1049 55

The pathophysiology of the postpartum blues, common transient mood disorders in the first week postpartum, has remained elusive. Recently, however, it has been shown that depression and anxiety disorders are accompanied by activation of the inflammatory response system (IRS). This study was developed to determine whether the postnatal blues is associated with IRS activation. Serum concentrations of interleukin-6 (IL-6), IL-6 receptor (IL-6R), gp130 (the IL-6 signaling protein), IL-1R antagonist (IL-1RA) and leukemia inhibitory factor receptor (LIFR) were assayed in 22 nonpregnant women and in 91 pregnant women before delivery and 1 and 3 days after delivery. On each occasion the parturient women completed the State version of the Spielberger State-Trait-Anxiety-Inventory (STAI) and the Zung Depression Rating Scale (ZDS). Serum IL-6, IL-1RA and LIFR were significantly higher in pregnant women at the end of term than in nonpregnant women.
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PMID:Immune activation in the early puerperium is related to postpartum anxiety and depressive symptoms. 1067 77

In a controlled study, such immunological parameters as whole blood production of the cytokines interleukin-6 (IL-6) and tumor-necrosis factor-alpha (TNF-alpha) were assessed in 24 inpatients with a major depressive disorder (MDD) both before and again under treatment. After a 6-week treatment period with amitriptyline, patients were classified as responders or nonresponders according to their psychopathological outcome as evaluated by the Hamilton and the Montgomery-Asberg Depression Rating Scales. Pre-treatment levels of c-reactive protein (CRP) were significantly higher in both patient subgroups than in the control subjects. In comparison to the controls, unstimulated pretreatment production of IL-6 was significantly decreased in the responders; whereas it was significantly increased in the nonresponder subgroup. Post-treatment values did not differ significantly among the patient and control groups. Pretreatment levels of TNF-alpha were increased in both patient subgroups, with a significant decrease during treatment only in the responder subgroup. Pretreatment levels of IL-6/10(5) mononuclear cells and the ratio between lymphocytes and monocytes acted as independent variables with regard to the clinical response. Our data indicate that unstimulated secretion of TNF-alpha is related to the psychopathological improvement; whereas, IL-6 levels might dichotomize the patients into subsequent responders and nonresponders already at admission.
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PMID:Cytokine production and treatment response in major depressive disorder. 1070 Jun 56

There is now some evidence that major depression is accompanied by activation of the inflammatory response system (IRS). Other signs of IRS activation, which have been reported in major depression are lowered serum zinc (Zn) and serum albumin (Alb) concentrations. In serum, Zn is closely bound to Alb. The aims of the present study were to replicate previous findings that major depression is accompanied by lowered serum Zn and Alb and to examine whether the decrease in serum Zn may be explained by that in serum Alb. The above variables were determined in 48 major depressed patients and in 15 age-sex-matched healthy volunteers. Serum Zn and Alb were significantly lower in major depressed patients than in normal volunteers. In healthy volunteers and major depressed patients, there were significant and positive correlations between serum Zn and Alb. We found that 53.8% of the variance in serum Zn could be explained by the combined effects of serum Alb and diagnostic classification. The results suggest that lower serum Zn in depression is in part explained by lowered serum Alb and by another depression-related mechanism. It is suggested that lower serum Zn in depression may be secondary to sequestration of metallothionein in the liver, which may be related to increased production of interleukin-6.
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PMID:Lower serum zinc in major depression in relation to changes in serum acute phase proteins. 1070 76

Retinoids have many pharmacological activities, including anti-inflammatory action and antiangiogenesis, effected through the regulation of various gene transcriptions. In this study, we investigated the effect of Am-80, one of the retinoic acid derivatives, on hapten-induced contact hypersensitivity in BALB/c mice. After application of 2,4-dinitrofluorobenzene (DNFB) to the ears of the mice, severe contact hypersensitivity with marked infiltration of inflammatory cells and hypertrophy of the epidermis was caused. The thickness of the ears increased biphasically and reached a peak 3 and 24 h after the DNFB challenge. Am-80 significantly inhibited ear thickness in the late-(24 h), but not the early-phase (3 h) reaction in a dose-dependent manner. In a histopathological study, obvious depression of edema and infiltration of inflammatory cells was observed in the ears of mice treated with Am-80. Am-80 inhibited the levels of expression in mice ears of interferon-gamma (IFN-gamma) and interleukin-6 (IL-6), but not tumor necrosis factor-alpha (TNF-alpha) or interleukin-4 (IL-4). Furthermore, Am-80 inhibited the antigen-induced production of some cytokines, including IFN-gamma and IL-6, but not IL-4, in vitro. Therefore, Am-80 inhibited hapten-induced contact hypersensitivity through the direct inhibition of inflammatory cytokines such as IFN-gamma and IL-6.
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PMID:Effect of Am-80, a retinoid derivative, on 2, 4-dinitrofluorobenzene-induced contact dermatitis in mice. 1082 46

The cachexia-anorexia syndrome occurs in chronic pathophysiologic processes including cancer, infection with human immunodeficiency virus, bacterial and parasitic diseases, inflammatory bowel disease, liver disease, obstructive pulmonary disease, cardiovascular disease, and rheumatoid arthritis. Cachexia makes an organism susceptible to secondary pathologies and can result in death. Cachexia-anorexia may result from pain, depression or anxiety, hypogeusia and hyposmia, taste and food aversions, chronic nausea, vomiting, early satiety, malfunction of the gastrointestinal system (delayed digestion, malabsorption, gastric stasis and associated delayed emptying, and/or atrophic changes of the mucosa), metabolic shifts, cytokine action, production of substances by tumor cells, and/or iatrogenic causes such as chemotherapy and radiotherapy. The cachexia-anorexia syndrome also involves metabolic and immune changes (mediated by either the pathophysiologic process, i.e., tumor, or host-derived chemical factors, e.g., peptides, neurotransmitters, cytokines, and lipid-mobilizing factors) and is associated with hypertriacylglycerolemia, lipolysis, and acceleration of protein turnover. These changes result in the loss of fat mass and body protein. Increased resting energy expenditure in weight-losing cachectic patients can occur despite the reduced dietary intake, indicating a systemic dysregulation of host metabolism. During cachexia, the organism is maintained in a constant negative energy balance. This can rarely be explained by the actual energy and substrate demands by tumors in patients with cancer. Overall, the cachectic profile is significantly different than that observed during starvation. Cachexia may result not only from anorexia and a decreased caloric intake but also from malabsorption and losses from the body (ulcers, hemorrhage, effusions). In any case, the major deficit of a cachectic organism is a negative energy balance. Cytokines are proposed to participate in the development and/or progression of cachexia-anorexia; interleukin-1, interleukin-6 (and its subfamily members such as ciliary neurotrophic factor and leukemia inhibitory factor), interferon-gamma, tumor necrosis factor-alpha, and brain-derived neurotrophic factor have been associated with various cachectic conditions. Controversy has focused on the requirement of increased cytokine concentrations in the circulation or other body fluids (e.g., cerebrospinal fluid) to demonstrate cytokine involvement in cachexia-anorexia. Cytokines, however, also act in paracrine, autocrine, and intracrine manners, activities that cannot be detected in the circulation. In fact, paracrine interactions represent a predominant cytokine mode of action within organs, including the brain. Data show that cytokines may be involved in cachectic-anorectic processes by being produced and by acting locally in specific brain regions. Brain synthesis of cytokines has been shown in peripheral models of cancer, peripheral inflammation, and during peripheral cytokine administration; these data support a role for brain cytokines as mediators of neurologic and neuropsychiatric manifestations of disease and in the brain-to-peripheral communication (e.g., through the autonomic nervous system). Brain mechanisms that merit significant attention in the cachexia-anorexia syndrome are those that result from interactions among cytokines, peptides/neuropeptides, and neurotransmitters. These interactions could result in additive, synergistic, or antagonistic activities and can involve modifications of transducing molecules and intracellular mediators. Thus, the data show that the cachexia-anorexia syndrome is multifactorial, and understanding the interactions between peripheral and brain mechanisms is pivotal to characterizing the underlying integrative pathophysiology of this disorder.
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PMID:Central nervous system mechanisms contributing to the cachexia-anorexia syndrome. 1105 8


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