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)

Although the clinical effects of acute exposure to ultraviolet (UV) light--such as cutaneous inflammation, malaise, somnolence, chills and fever--have been appreciated many years, the underlying mechanisms mediating these effects are poorly understood. Interleukin-6 (IL-6) is a potent cytokine with a wide variety of biologic activities, including induction of fever and acute phase response. Because IL-6 is produced by keratinocytes in vivo and in vitro and because the release is enhanced by UV light, the present study was performed to investigate the effect of a single UV dose eliciting moderate to severe sunburn reaction on the production of IL-6 in vivo. Therefore, plasma of UV-treated human subjects was evaluated for IL-6 activity by testing its capacity to induce the proliferation of an IL-6-dependent hybridoma cell line (B9). In contrast to plasma samples obtained before UV exposure, post-UV-specimens contained significant levels of IL-6 peaking at 12 h after UV irradiation. Plasma IL-6 activity was neutralized by an antiserum directed against recombinant human IL-6, and upon HPLC gel filtration exhibited a molecular weight of around 20 kD. Moreover, plasma IL-6 levels correlated remarkably with fever course followed by an increase of acute phase proteins such as C-reactive protein. These data indicate that IL-6, which is released by keratinocytes following UV exposure, may gain access to the circulation and via its pyrogenic as well as acute phase-inducing effect may function as an important mediator of systemic sunburn reaction.
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PMID:Ultraviolet light induces increased circulating interleukin-6 in humans. 235 83

We have used a chimeric monoclonal anti-CD4 antibody (cM-T412) in a phase I trial involving patients with refractory RA. The objectives of this initial study were to evaluate the safety, immunogenicity, and biologic effects of cM-T412. Twenty-five patients with active refractory RA (all taking methotrexate concomitantly) were treated with incremental doses (10 to 700 mg) of cM-T412 in an open-label, escalating dose phase I trial. Levels of circulating CD4+ T-cells decreased rapidly post-infusion and remained significantly depressed even at 18 months following treatment. Repopulation of CD4+ T cells consisting of increased CD45RA+ (naive) and CD45RO+ (memory) CD4+ T-cells was observed in approximately 1/3 of the patients between day 14 and 6 months post-infusion. Proliferative responses of peripheral blood lymphocytes to mitogens and recall antigens were generally diminished following cM-T412 infusion, with mitogen responses normalizing more rapidly than responses to recall antigens. Adverse events during the first 6 months of follow-up included fever, often associated with myalgias, malaise, and asymptomatic hypotension; these symptoms were self-limited and appeared to correlate with transient elevations of interleukin-6. Negligible human antibody responses to the cM-T412 variable region were observed; indeed, only 2 patients developed transient low levels of antibodies reactive with cM-T412. Non-blinded assessment indicated that 43% of patients exhibited > or = 50% improvement in tender joint counts at 5 weeks, and 33% at 6 months post-infusion.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Experience with a chimeric monoclonal anti-CD4 antibody in the treatment of refractory rheumatoid arthritis. 810 Jul 52

Inhalation of swine dust induces airway inflammation and general symptoms, such as fever and malaise. In the present investigation, the presence and time course of changes in tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) in serum were studied to evaluate possible mechanisms by which inhalation of swine dust induces general symptoms. A group of 14 previously nonexposed subjects weighed swine for 3 h. The average +/- SD inhalable dust concentration was 22.4 +/- 4.7 mg/m3 and endotoxin, 1.2 +/- 0.4 microgram/m3. TNF-alpha in serum increased from 2.5 (1.8 to 3.1) ng/L (median, interquartile range) before exposure to maximum values 10.0 (4.6 to 15.7) ng/L between 3 and 5 h after the start of exposure. IL-6 increased from less than 1.5 to 21.4 (18.6 to 33.6) ng/L 4 to 11 h after the start of exposure. Maximum IL-6 occurred 1 to 5 h after the maximum TNF-alpha. In many subjects, however, an early rise in IL-6 parallel to the change in TNF-alpha was seen. The results that some of the peripheral reactions to swine dust might be mediated by TNF-alpha and IL-6. The early rise in IL-6 implies multiple origins of the IL-6.
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PMID:Time course of interleukin-6 and tumor necrosis factor-alpha increase in serum following inhalation of swine dust. 854 8

Two young adult patients with typical virus-associated haemophagocytic syndrome (VAHS) were treated with cyclosporin A and granulocyte colony-stimulating factor (G-CSF). Clinical symptoms such as high fever and malaise disappeared rapidly with concurrent haematological improvement in both patients. The serum levels of interleukin-6 (IL-6), soluble IL-2 receptor, tumour necrosis factor and macrophage-CSF were all elevated before treatment but that of G-CSF was not. The dramatic effect of cyclosporin A observed implies that it efficiently and rapidly suppresses the cytokine storm caused by dysregulated T cells in VAHS. In addition, G-CSF may promote haematological recovery without syndrome regression. We believe that the combination of cyclosporin A and G-CSF may be effective, at least in selected patients with VAHS. Further studies are required to confirm its role as first-line therapy for adult patients with VAHS.
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PMID:Successful treatment of virus-associated haemophagocytic syndrome in adults by cyclosporin A supported by granulocyte colony-stimulating factor. 916 30

In patients with Lyme neuroborreliosis, inflammation and symptoms of fatigue and malaise occur out of proportion to the relatively low number of spirochetes present. Previous studies have identified interleukin-6 (IL-6) as a candidate molecule for amplification of CNS inflammation in this disease. We pursued this possibility by measuring cytokine gene expression by reverse-transcriptase polymerase chain reaction (RT-PCR) in the brain of rhesus macaques actively infected with Borrelia burgdorferi. Samples of brain tissue were screened for IL-6 and interferon gamma using RT-PCR-ELISA, a technique that uses RT-PCR, subsequent hybridization of the PCR product with a biotinylated probe, and capture and ELISA readout of hybridization product. The number of copies in positive samples was then quantitated using qRT-PCR-ELISA, in which wild-type cytokine cDNA competes with recombinant competitor DNA in the PCR. Elevated levels of IL-6 cDNA and, to a lesser extent, interferon gamma were detected in three of three nonhuman primates with persistent infection with B burgdorferi, whereas the brains of three uninfected animals and undetectable levels of gene expression of these cytokines. These data support the hypothesis that cytokines such as IL-6 are important amplification molecules for CNS inflammation in Lyme neuroborreliosis.
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PMID:Interleukin-6 is expressed at high levels in the CNS in Lyme neuroborreliosis. 922 83

The goal of this study was to evaluate, in patients with prostate cancer, the toxicity profile and biologic activity of the bispecific antibody MDXH210, which has specificity for the non-ligand-binding site of the high-affinity immunoglobulin G receptor (Fc gamma RI) and the extracellular domain of the HER-2/neu proto-oncogene product. Patients with prostate cancer that expressed HER-2/neu were entered into a phase I dose-escalation trial of MDXH210. Patients received an intravenous infusion MDXH210 during a period of 2 h three times per week for 2 weeks and were monitored for toxicity. Pharmacokinetic and pharmacodynamic parameters were measured and included the biologic end points of monocyte-bound MDXH210, cytokine production, and clinical response. Seven patients were treated with MDXH210 doses ranging from 1 to 8 mg/m2. In general, MDXH210 was well tolerated, with only mild infusion-related malaise, fever, chills, and myalgias. No dose-limiting toxic effects were observed. Biologic effects included induction of low plasma concentrations of tumor necrosis factor-alpha and interleukin-6 observed immediately after MDXH210 infusion and 70% saturation of circulating monocyte-associated Fc gamma RI with MDXH210 at a dose level of 4 to 8 mg/m2. Five of six patients had stable prostate-specific antigen levels during the course of 40 days or more. Circulating plasma HER-2/neu levels decreased by 80% at days 12 and 29 (p = 0.03 and 0.06, respectively, by the Wilcoxon signed rank test). MDXH210 can be given safely to patients with HER-2/neu-positive prostate cancer in doses of at least 8 mg/m2. At the doses studied, biologic activity was demonstrated and characterized by binding of MDXH210 to circulating monocytes, release of monocyte-derived cytokines, a decrease in circulating HER-2/neu, and short-term stabilization of prostate-specific antigen levels.
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PMID:Phase I pilot trial of the bispecific antibody MDXH210 (anti-Fc gamma RI X anti-HER-2/neu) in patients whose prostate cancer overexpresses HER-2/neu. 1121 Nov 51

We analyzed a series of 112 consecutive cases of left atrial myxoma diagnosed in a single French hospital (72 women and 40 men; age range, 5-84 yr) over 40 years, from 1959 to 1998. Symptoms of mitral valve obstruction, the first arm of the classic triad of myxoma presentation, were present in 75 patients (67%), with mostly cardiac failure or malaise. Symptoms of embolism, the second frequent presentation in the classic triad, were observed in 33 cases (29%) with 1 or several locations, essentially cerebral emboli with stroke. Males are statistically at greater risk than females of developing embolic complications. The third arm of the classic triad consists of constitutional symptoms (34%) with fever, weight loss, or symptoms resembling connective tissue disease, due to cytokine (interleukin-6) secretion. Younger and male patients have more neurologic symptoms, and female patients have more systemic symptoms. Seventy-two patients (64%) had cardiac auscultation abnormalities, essentially pseudo-mitral valve disease (53.5%) and more rarely the suggestive tumor plop (15%). The most frequent electrocardiographic sign was left atrial hypertrophy (35%), whereas arrhythmias were uncommon. The greater number of myxoma patients (98) diagnosed preoperatively after 1977 reflects the introduction of echocardiography as a noninvasive diagnostic procedure. However, there was no significant reduction in the average time from onset of symptoms to operation between patients seen in the periods before and after 1977. The tumor diameter ranged from 1 to 15 cm with a weight of between 15 and 180 g (mean, 37 g). The myxoma surface was friable or villous in 35% of the cases, and smooth in the other 65% cases. Myxomas in patients presenting with embolism have a friable surface; those in patients with cardiac symptoms, pseudo-mitral auscultation signs, tumor plop, and electrocardiogram or radiologic signs of left atrium hypertrophy and dilatation are significantly the larger tumors. The long-term prognosis is excellent, and only 4 deaths occurred among our 112 cases over a median follow-up of 3 years. The recurrence rate is low (5%), but long-term follow-up and serial echocardiography are advisable especially for young patients.
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PMID:Clinical presentation of left atrial cardiac myxoma. A series of 112 consecutive cases. 1138 92

Intravenous immune gamma-globulin (IVIG) is used successfully in the treatment of Kawasaki disease, with dose-dependent rapid resolution of symptoms such as fever and irritability and a decrease in ESR, WBCs, and platelets. The mode of action of IVIG in reducing this inflammatory response is not clearly understood. Recently anticytokine antibodies in IVIG have been demonstrated. Serum levels of proinflammatory cytokines have been shown to be elevated in patients with Kawasaki disease. The cytokine interleukin-6 (IL-6) is involved in the de novo production of acute-phase proteins by hepatocytes and cause thrombocytosis and fever in response to tissue injury. Patients receiving parenteral recombinant human IL-6 have dose-dependently experienced fever, malaise, chills, and acute-phase reaction. With high IL-6 concentrations, central nervous system toxicity has also been reported and IL-6 has been thought to mediate endothelial damage. We evaluated the response of stimulated blood cells of 12 normal children to IVIG in the release of the cytokines IL-6, IL-8, TNF-alpha. and IL-6 receptor (sIL-6R). The levels of cytokines IL-6, IL-8, and TNF-alpha (but not sIL-6R) in peripheral blood induced by stimulation with LPS were markedly reduced (P < 0.008) within 3 hr when incubated with IVIG compared to without IVIG. Thus we demonstrated that cells of normal children respond to IVIG in vitro by reducing cytokines such as IL-8, TNF-alpha, and IL-6 without affecting the level of receptor sIL-6R during an acute inflammatory response. We also found significantly higher IL-6 levels in children with Kawasaki disease compared to children with blood culture-negative febrile illnesses. In five children with Kawasaki disease we measured serum IL-6 before and after IVIG and assessed the clinical response to IVIG therapy. Therapy with IVIG was followed by a rapid resolution of symptoms in Kawasaki disease, with a significant decrease in serum IL-6. The attenuation of proinflammatory cytokine responses, especially IL-6, following infusions of IVIG may play an integral role in the rapid resolution of symptoms and decrease in the acute-phase proteins in children with Kawasaki disease. Cells of normal children were found to respond to the IVIG in a manner similar to that of the Kawasaki children.
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PMID:Cytokine modulation with immune gamma-globulin in peripheral blood of normal children and its implications in Kawasaki disease treatment. 1140 26

We report a case of central nervous system (CNS) lupus showing peculiar findings on cranial magnetic resonance imaging (MRI) with remarkable improvement after corticosteriod therapy. The patient was a 28-year-old woman, admitted to our hospital with severe fever, general malaise, and facial edema on June 4, 2001. After admission, she was diagnosed with systemic lupus erythematosus (SLE). On June 6, she showed diplopia at a distance, and on June 10, she suddenly became unconscious and developed general convulsions. Cranial MRI showed asymmetrical, multifocal, high signal intensity lesions on T2-weighted image (T2-WI) and low signal intensity on T1-weighted image (T1-WI). These lesions were primarily present in the subcortical white matter, with some detected in the overlying cerebral cortex. Gadolinium (Gd)-DTPA enhanced T1-WI showed marked leptomeningeal enhancement overlying the lesions on T1-WI and T2-WI. Apparent diffusion coefficient image (ADCI) showed high signal intensity in the surrounding areas of the T1-WI and T2-WI lesions, and low signal intensity in the central areas of the lesions. Diffusion weighted image (DWI) showed high signal intensity in the central areas of the low signal intensity on ADCI. Cerebrospinal fluid (CSF) examination revealed albuminocytologic dissociation (cell counts of 2/microliter and protein level of 108 mg/dl). CSF IgG index was elevated to 1.152 (normal < 0.7) and interleukin-6 (IL-6) activity to 27.2 pg/ml (normal < 4.0). On June 10, Intravenous administration of high-dose methylprednisolone (1,000 mg/day for 3 days) was started to treat CNS lesions of SLE. Her CNS manifestations, CSF findings, and the lesions on the cranial MRI improved remarkably. This is the first case report describing the lesions on both ADCI and DWI in a case of CNS lupus. The findings of ADCI and DWI suggest that the lesions of high signal intensity on ADCI indicate interstitial edema caused by inflammatory microangiopathy, and the lesions of high signal intensity on DWI and low signal intensity on ADCI indicate cytotoxic edema caused by ischemic change resembling microinfarction. We speculate that in addition to usual T1-WI and T2-WI, performing ADCI and DWI is useful for understanding the pathogenesis of CNS lupus lesions, and may play a significant role in the prognosis.
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PMID:[A central nervous system lupus showing peculiar findings on cranial magnetic resonance imaging (MRI)]. 1458 67

Parathyroid hormone-related protein (PTHrP) plays a central role in humoral hypercalcemia of malignancy (HHM), which is one of the most frequent paraneoplastic syndromes. PTHrP produced by the tumor acts through a common PTH/PTHrP receptor to promote bone resorption, inhibit calcium excretion from the kidney, and induce hypercalcemia. Patients with HHM often develop cachexia associated with typical symptoms such as anorexia, malaise, nausea, constipation, polyuria, polydipsia, and confusion. The etiology of the cachexia is not fully understood but is thought to be caused by hypercalcemia and various cytokines such as interleukin-6, tumor necrosis factor-alpha, leukemia inhibitory factor, and others. In this study, we investigated the role of PTHrP in hypercalcemia and cachexia in HHM by using humanized anti-PTHrP antibody. A mouse monoclonal antibody that binds to PTHrP amino acid sequence 1-34 and inhibits PTHrP function has been humanized to create a specific and potent agent for the treatment of patients with HHM. The mouse monoclonal antibody has been shown to have antihypercalcemic activity against nude mice bearing human tumors. Because a mouse antibody is highly immunogenic in human patients, the complementarity-determining regions from the mouse antibody were grafted into a human antibody. The resulting humanized antibody specifically recognizes PTHrP(1-34) and neutralizes PTHrP functions in vitro and in vivo. The humanized anti-PTHrP antibody was administered intravenously to HHM model animals bearing tumors such as LC-6 human lung carcinoma. These animals showed symptoms similar to those of patients with HHM (eg, hypercalcemia and cachexia). The humanized anti-PTHrP antibody-treated animals responded with normalization of blood ionized calcium level through an improvement of bone metabolism and calcium excretion. Moreover, the treated animals also showed an improvement in body weight, ultromotivity, metabolic alkalosis, food consumption, water intake, serum phosphorus, and renal function. Consequently, the humanized antibody-treated animals experienced complete resolution of hypercalcemia and cachexia. These results suggest that the humanized antibody would be an effective and beneficial agent for patients with HHM, and that PTHrP is a major pathogenetic factor of hypercalcemia and cachexia in patients with HHM.
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PMID:Treatment of malignancy-associated hypercalcemia and cachexia with humanized anti-parathyroid hormone-related protein antibody. 1461 38


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