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)

The development of an onchocercal chorioretinopathy from the first detectable signs to a full blown oncho fundus is not fully understood. We investigated the intraocular humoral immune response against Onchocerca volvulus, human S-antigen, IRBP and crude retinal extract (using an ELISA) by examining paired aqueous humour and serum samples obtained from onchocerciasis patients (without [n = 10] and with ocular symptoms [n = 8]) and endemic controls [n = 14] from Sierra Leone (West Africa). A local intraocular anti-retinal IgG antibody production could not be demonstrated in onchocerciasis patients, whether they had ocular symptoms or not. A significantly higher level of O. volvulus antibodies and IgG was measured in the aqueous of onchocerciasis patients with ocular involvement, as compared to patients without ocular symptoms (Mann-Whitney ranksum test; p less than 0.001 and p less than 0.02 respectively). Since interleukin-6 (IL-6) plays an essential role in the differentiation of B cells into immunoglobulin producing plasma cells, we therefore measured this cytokine in paired aqueous and serum samples. Elevated IL-6 levels were found in the aqueous of two out of eight onchocerciasis patients tested. In view of these findings it seems improbable that retinal autoimmunity is a major factor in the pathogenesis of onchocercal chorioretinopathy. The high intraocular levels of antibodies against the parasite suggest a direct involvement of the parasite in the pathogenesis of onchocercal chorioretinopathy.
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PMID:Analysis of aqueous humour in ocular onchocerciasis. 203 8

Forty-one African patients suffering from clinically defined severe malaria were studied in the intensive medical care unit of the main hospital in Dakar, Senegal, West Africa. All of these individuals lived in Greater Dakar, an area of low and seasonal Plasmodium falciparum endemicity. Twenty-seven patients (mean age +/- 1 standard deviation, 19.2 +/- 12.7 years) survived this life-threatening episode, but 14 (30.8 +/- 16.2 years old) died despite initiation of adequate treatment. On the day of admission (day 0) and 3 days later, one to two blood samples (i.e., approximately 10 to 15 ml) were obtained from each subject, and different biological parameters were evaluated in the two groups. Plasma samples were tested for their content in tumor necrosis factor alpha (TNF-alpha), soluble receptors I and II for TNF-alpha (TNF-alpha sRI and TNF-alpha sRII), interleukin-6 (IL-6), IL-6 sR, IL-10, and IL-2 sR. The concentrations of all these cytokines and/or their receptors was significantly elevated in patient plasma samples on day 0, and it rapidly decreased in the group of individuals who survived. By comparison, the mean concentration of the same parameters decreased slowly in the group of patients who died (except for IL-10, which dramatically fell in all patient plasma samples soon after initiation of antimalarial treatment). The TNF-alpha sRI level remained significantly elevated among the patients who died, and the highest levels of soluble TNF-alpha sRI receptor were found among the older patients. Parasite-specific immunoglobulin M (IgM), total IgG, IgG1, IgG2, IgG3, and IgG4 were evaluated by enzyme-linked immunosorbent assay using a crude extract of a local P. falciparum isolate as antigen and human class- and subclass-specific monoclonal antibodies. Parasite-specific IgM, total IgG, and IgG1 were detectable in the plasma samples of most of these African patients, whereas IgG2 and IgG4 mean values were low. The mean level of parasite-specific IgG3 was different (P = 0.024) at day 0, i.e., before initiation of intensive medical care, between the group of the 27 surviving subjects and the group of 14 patients dying of severe malaria. As a consequence, most of the African patients who died had only trace amounts or almost no detectable level of parasite-specific IgG3 at the time of admission. In contrast, the presence of even limited IgG3 activity at day 0 was found to be associated with a significantly increased probability of recovering from severe malaria. Therefore, in our study, both an elevated level of TNF-alpha sRI and absence of IgG3 activity were of bleak prognostic significance, whereas a favorable outcome was usually observed when parasite-specific IgG3 activity was detectable. This finding was strongly suggestive of a prime role for these parasite-specific immunoglobulins in the capacity to help recovery from severe malaria.
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PMID:Prognostic value of anti-Plasmodium falciparum-specific immunoglobulin G3, cytokines, and their soluble receptors in West African patients with severe malaria. 923 86

Systemic inflammatory response syndrome (SIRS) is one of the most common causes of death in intensive care unit patients. The detoxification plasma filtration (DTPF) system (HemoCleanse, Inc., West Lafayette, IN) combines the DT hemodiabsorption system in series with a push-pull pheresis PF system (a suspension of powdered sorbents surrounding 0.5 microm plasma filter membranes). Bidirectional plasma flow (at 80-100 ml/min) across the PF membranes provides direct contact between plasma proteins and powdered sorbents, as well as clearance of cytokines (tumor necrosis factor-alpha, interleukin-1beta, and interleukin-6) at a rate of 15-25 ml/min, without evidence of saturation for 90 minutes. In a U.S. Food and Drug Administration approved study we treated eight patients with SIRS and organ failure with a single DTPF treatment, using powdered charcoal as sorbent in four patients and powdered charcoal and silica in four patients. Treatments proceeded for 6 hours with proper heparin anticoagulation (activated clotting time 250-300 sec) and appeared safe. All patients improved during the treatments and each had increased blood pressure and decreased need for pressor agents. Plasma cytokine levels stabilized or decreased during treatment and were significantly lower the morning after treatment. Multiple organ dysfunction (MOD) and Acute Physiology Chronic Health Evaluation II scores and organ function gradually improved in most patients, and two patients survived for more than 28 days and two for more than 14 days. The DTPF System may prove beneficial in treatment of patients with sepsis.
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PMID:Systemic inflammatory response syndrome treatment by powdered sorbent pheresis: the BioLogic-Detoxification Plasma Filtration System. 980 17

We have examined four polymorphic elements in the human interleukin-6 (IL-6) locus and described their allele distribution in 73 unrelated, healthy individuals from the West-of-Scotland. These comprised three single nucleotide polymorphisms (SNP) in the 5' promoter region of the gene and one VNTR in the 3' region of IL-6. A statistical consideration of the relationship between alleles at each locus was carried out. Of a total of 12 possible haplotypes observed in the population, the analysis suggested that four were prominent. These accounted for 41.1%, 28.1%, 14.4% and 3.4% respectively; in total, 87% of the haplotypes present. Frequently, these proposed haplotypes were supported by homozygosity across all four loci within individuals. We propose that these haplotypes be identified as IL6.0103, IL6.0204, IL6.0207 and IL6.0307, in recognition of their frequency in this population and the alleles that they contain.
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PMID:Allele associations reveal four prominent haplotypes at the human interleukin-6 (IL-6) locus. 1119 76

In the present study, we have tested the ability of coal dust to stimulate kinase phosphorylation of activator protein-1 (AP-1) signal transduction pathways and production of interleukin-6 (IL-6) in both mouse epidermal JB6 and human lung epithelial A549 cells. Seven coal samples from three coalmine regions of Pennsylvania (PA), West Virginia (WV), and Utah (UT) with high, medium, and low prevalence of coal workers' pneumoconiosis (CWP), respectively, were investigated. Results from the present study indicate that three PA coals stimulated the mitogen-activated protein kinase (MAPK) family of extracellular signal-regulated kinases (ERKs) and p38 MAPK, but not c-Jun-NH2-terminal kinases (JNKs) in human lung A549 cells. The effects of three UT coals on the kinase phosphorylation were less as compared to those of the PA coals. Coal dusts from three coalmine regions induced IL-6 in a dose-dependent manner in both JB6 and A549 cells. Interestingly, levels of IL-6 in both cells treated with coals from three coalmine regions correlated well with CWP prevalence from that region. To assess the role of AP-1 pathways in coal-mediated transcriptional activation of IL-6, various inhibitors were used in cells treated with one PA coal, which induced a maximal response. It was found that the increase in IL-6 protein and mRNA by the PA coal was completely eliminated by the pretreatment of both cell types with PD98059, a specific MEK1 inhibitor, and SB202190, a p38 kinase inhibitor. Our results indicate that coal dust can stimulate IL-6 release from mouse epidermal JB6 cells and human lung epithelial A549 cells, and the coal-induced IL-6 increase may involve ERKs and p38 MAPK pathways.
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PMID:Coal-induced interleukin-6 gene expression is mediated through ERKs and p38 MAPK pathways. 1291 2

Elevated cytokine response has been reported in patients with epileptic seizures. The objective of this study was to investigate the possible role of interleukin-6 (IL-6) in the pathogenesis of infantile spasms in West syndrome (WS). We measured IL-6 levels in cerebrospinal fluid (CSF) obtained from the newly diagnosed patients with WS. Twelve patients with WS (Group I) were classified as symptomatic WS (Group IA) in eight and as cryptogenic WS (Group IB) in four. The results were compared with control groups including patients with tonic-clonic seizures associated with two different kind of inflammation of central nervous system; Group IIA (infection): bacterial meningitis/encephalitis and Group IIB (trauma): post-traumatic seizures. There was no statistically significant difference between the mean values of CSF IL-6 levels in patients with WS (2.95 +/- 2.31 pg/ml) and those of subgroups of WS (Group IA: 2.26 +/- 2.01 pg/ml and Group IB: 4.33 +/- 2.52 pg/ml). Both control groups had highly increased IL-6 levels in CSF (Group IIA: 193.05 +/- 185.52 pg/ml and Group IIB: 112.74 +/- 167.44 pg/ml) than those of the patients with WS. Elevated IL-6 response in patients with tonic-clonic seizures associated with inflammation of central nervous system might be due to the seizures themselves or related to the underling etiology (infection or trauma). However, no elevated IL-6 response was found in patients with infantile spasms.
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PMID:Cerebrospinal fluid interleukin-6 levels in patients with West syndrome. 1596 15

Bone deposition, for any implant system, is the deciding factor for the success. The biochemical signals at the cellular level will help elucidate the direction of host response. In this report, intercellular messenger, cytokines, that are regulatory for osteoblast and osteoclast function, were measured. Production of osteocalcin, a marker for osteoblast maturation was also estimated. Human osteoblast-like cells from osteosarcoma cell line MG 63 were grown in wells in the presence of titanium (Ti), titanium alloy (Ti6A14V) and stainless steel implant materials incubated at 37 degrees C. Interleukin-1alpha (IL-1alpha), IL-6, IL-8, IL-11 and osteocalcin were quantitated using standard enzyme linked immunosorbant assay (ELISA) kits from the growth media extracted at specific intervals over the critical ten day period. In all dishes, cells were seen adhering to the base after 24 hours and to confluence at 96 hours. Both IL-1alpha and IL-11 were not produced in sufficient quantities to be measured in the assay (< pg/ml). Interleukin-6 production was significantly higher for stainless steel than for titanium and the alloy. There was a progressive rise in osteocalcin production for titanium contrasted to a basal rate for stainless steel and alloy. Interleukin-8 levels for all metals and controls increased markedly after two days implicating inherent cellular characteristics. A relatively high constant range for macrophage colony stimulating factor from the first day was seen for all metals, including the controls. In conclusion, it appears that titanium implants activate osteocalcin production while stainless steel activates IL-6.
West Indian Med J 2005 Sep
PMID:An in vitro comparison of implant materials cell attachment, cytokine and osteocalcin production. 1631 93

Idiopathic osteolysis is a very rare bone condition of unknown origin. The length of the illness usually lasts for several years. The purpose of this paper is to point out the possibility of severely rapid progression of idiopathic osteolysis and to contribute to a better understanding of the natural history of Gorham-Stout disease. We report the case of a 58-year old man whose right humeral head and lateral clavicle had disappeared as a result of massive osteolysis observed only six months after onset of the symptoms. Such rapid progression has not been reported previously. His physical examination was otherwise normal. Serum interleukin-6 (IL-6) was elevated and the other laboratory tests were normal. Radiography, computed tomography scan, bone scan, and magnetic resonance imaging (MRI) evaluation revealed extensive destruction of the right humeral head and lateral clavicle involving the acromioclavicular joint. Although the histologic features could not be confirmed because the patient refused a biopsy, it was felt that the patient satisfies the other diagnostic features of Gorham-Stout disease. Follow-up examinations revealed no further bone or soft-tissue involvement. Gorham-Stout disease should be considered in the differential diagnosis of such severely rapid progression of lytic bony lesions.
West Indian Med J 2006 Oct
PMID:Rapid idiopathic osteolysis of the humeral head and clavicle. 1737 6

Seizures are a major complication of viral encephalitis. However, the mechanisms of seizure-associated neuronal dysfunction remain poorly understood. We report that intranasal inoculation with West Nile virus (WNV) (Sarafend) causes limbic seizures in C57BL/6 mice, but not in interferon (IFN)-gamma-deficient (IFN-gamma-/-) mice. Both strains showed similar levels of virus in the brain, as well as similar concentrations of the cytokines, tumor necrosis factor and interleukin-6, both of which can alter neuronal excitability. Experiments in chimeric IFN-gamma-/- mice reconstituted with IFN-gamma-producing leukocytes showed that IFN-gamma is not required during central nervous system infection for limbic seizure development, suggesting a role for IFN-gamma in the developing brain. This was supported responses to pentylenetetrazole, kainic acid (KA), and N-methyl-d-aspartate (NMDA). Both strains of mice exhibited similar behavior after pentylenetetrazole challenge. However, while NMDA and KA treatment resulted in characteristic seizures in C57BL/6 mice, these responses were diminished (NMDA treatment) or absent (KA treatment) in IFN-gamma-/- mice. Furthermore, NMDA-receptor blockade with MK-801 in WNV-infected C57BL/6 mice abrogated seizures and prolonged survival. Our data show that IFN-gamma plays an important role in the development of the excitatory seizure pathways in the brain and that these cascades become pathogenic in encephalitic WNV infection.
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PMID:Role of IFN-gamma in an experimental murine model of West Nile virus-induced seizures. 1785 52

The innate immune response is the first line of defense against foreign pathogens. The recognition of virus-associated molecular patterns, including double- and single-stranded RNA, by pattern recognition receptors initiates a cascade of signaling reactions. These result in the transcriptional upregulation and secretion of proinflammatory cytokines that induce an antiviral state. Many viruses have evolved mechanisms to antagonize these responses in order to help them establish a productive infection. We have previously shown that West Nile virus (WNV) is able to inhibit Toll-like receptor 3 (TLR3)-mediated activation of interferon (IFN) regulatory factor 3 (IRF3) (F. Scholle and P. W. Mason, Virology 342:77-87, 2005). In the present study, the WNV nonstructural (NS) proteins were analyzed individually for their ability to antagonize signal transduction mediated by TLR3. We report that expression of WNV NS1 inhibits TLR3-induced transcriptional activation of the IFN-beta promoter and of an NF-kappaB-responsive promoter. This inhibition was due to a failure of the TLR3 ligand poly(I:C) to induce nuclear translocation of IRF3 and NF-kappaB. Furthermore, NS1 expression also inhibited TLR3-dependent production of interleukin-6 and the establishment of an antiviral state. The function of NS1 in flavivirus infection is not well understood. NS1 is required for viral RNA replication and is also secreted from mammalian cells but not from insect cells. Here, we identify a previously unrecognized role for NS1 in the modulation of signaling pathways of the innate immune response to WNV infection.
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PMID:West Nile virus nonstructural protein 1 inhibits TLR3 signal transduction. 1856 33


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