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

A study was conducted to determine whether serum interleukin-6 (IL-6) activity increased in horses during experimentally induced endotoxemia and whether serum IL-6 activity correlated to changes in clinical or laboratory data. Six clinically normal horses were given endotoxin IV (30 ng/kg of body weight) in 0.9% NaCl solution over 1 hour. Five of these and 1 additional horse served as controls and were given only 0.9% NaCl solution. Venous blood, for determination of serum IL-6 activity and WBC count, was collected before and at various times through 8 hours after the start of endotoxin or NaCl infusion. Rectal temperature and heart and respiratory rates were recorded throughout the study period. Serum IL-6 activity was determined by bioassay of proliferation of the B13.29 clone B.9 hybridoma cell line. From 1.5 through 5 hours after start of the infusion, serum IL-6 activity was significantly (P less than 0.05) increased in horses given endotoxin. Mean peak serum IL-6 activity was observed between 3 and 4 hours. In response to endotoxin infusion, horses became lethargic, tachycardic, and febrile. Leukopenia developed by 1 hour, followed by leukocytosis at 8 hours. Significant (P less than 0.05) positive association and linear correlation were apparent between mean serum IL-6 activity and mean rectal temperature in the group of horses that were given endotoxin. Changes from baseline were not evident in any of the clinical or laboratory values in horses given only NaCl solution.
 ...
PMID:Effect of experimentally induced endotoxemia on serum interleukin-6 activity in horses. 152 1

30 patients with chemotherapy-related leukopenia (white cells 1.0 x 10(9)/l or lower) and fever (temperature 38.5 degrees C or higher) were treated in a double-blind randomised trial with standard antibiotics and 7 days of intravenously administered recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF, 2.8 micrograms/kg per day) or placebo. GM-CSF administration resulted in a faster percentage increase of peripheral neutrophil count after 2 and 3 days of treatment, except in patients treated with ablative chemotherapy and autologous bone-marrow transplantation. However, GM-CSF did not shorten the period of fever or antibiotic administration. No side-effects were observed; in particular tumour necrosis factor alpha and interleukin-6 did not increase in the 5 GM-CSF patients tested. These data suggest that a subgroup of patients with chemotherapy-related leukopenia and fever may benefit from GM-CSF treatment in view of the observed effects on neutrophil count.
 ...
PMID:Efficacy and tolerability of recombinant human granulocyte-macrophage colony-stimulating factor in patients with chemotherapy-related leukopenia and fever. 214 17

Interleukin-6 (IL-6) has been shown to be an inducer of the acute-phase response (APR) and to be involved in the pathogenesis of several disease states, including graft-versus-host disease (GvHD) following allogeneic bone marrow transplantation (BMT). As blood cells of the monocyte lineage are known to be major producers of this cytokine, we wondered whether extreme peripheral leukopenia following total ablation of hematopoiesis could compromise IL-6 production during the first days after allogeneic or autologous BMT. In the absence of detectable circulating leukocytes we measured elevated IL-6 levels in six children having fever (> or = 38 degrees C) of presumed infectious origin with an average of 74 +/- 60 units/ml (range 19-309 units/ml). IL-6 levels in febrile children having a normal hematopoiesis (118 +/- 254 units/ml, range 17-1213 units/ml) were not significantly higher than those found in the febrile BMT group (p > 0.05). Moreover, there was a clear association between elevated IL-6 levels and the presence of fever. C-reactive protein (CRP) was also elevated (> or = 1 mg/dl), whereas tumor-necrosis factor alpha (TNF) was undetectable (< 1 pg/ml). Two transplanted patients without fever during the period of total aplasia had neither detectable CRP nor IL-6, thus demonstrating that the transplant procedure itself does not induce an APR. Our data obtained during maximal leukopenia following BMT show that a functional hematopoietic system is not necessary for regular production of IL-6, which is associated with fever. Cells of nonhematopoietic origin may contribute to this production.
 ...
PMID:Interleukin-6 (IL-6) levels in febrile children during maximal aplasia after bone marrow transplantation (BMT) are similar to those in children with normal hematopoiesis. 763 10

Previous reports have indicated that immunological priming of animals will result in increased cytokine production and enhanced susceptibility to the toxicity of cytokines. We primed mice with complete Freund's adjuvant and challenged 2 weeks later with 1 mg/mouse of lipopolysaccharide. Primed mice produced less tumor necrosis factor than naive mice (35 +/- 8 vs 108 +/- 20 ng/ml) and also less interleukin-6 (182 +/- 37 vs 6.39 +/- 155 ng/ml). Leukopenia developed only in the naive mice. Although neutropenia and lymphocytosis developed in both groups, the alterations manifested themselves more quickly in primed mice. Primed mice had substantially greater pulmonary neutrophil sequestration determined both enzymatically and histologically but no lung damage. However, primed mice had significantly less small bowel damage than naive mice. Mortality was substantially reduced in primed mice compared with unprimed mice. These results demonstrate that immunological priming in vivo decreases cytokine production in response to lipopolysaccharide challenge, decreases organ injury, and reduces mortality.
 ...
PMID:Immunological priming attenuates the in vivo pathophysiological response to lipopolysaccharide. Comparison of cytokine production, tissue injury, and lethality in complete Freund's adjuvant-primed mice and in unprimed mice. 812 45

Human neutrophil azurophilic granules contain an approximately 55-kDa protein, known as bactericidal/permeability-increasing protein (BPI), which possesses a high-affinity binding domain for the lipid A component of lipopolysaccharide (LPS). The in vivo LPS neutralizing activity of exogenous BPI was studied in a model of lethal Escherichia coli bacteremia. Five baboons were treated with BPI (5 mg/kg bolus injection followed by a 95 micrograms/kg/min BPI infusion over 4 hr), while four additional animals received a genetically engineered variant of BPI (NCY103). Five animals received a placebo treatment and served as controls. Both wild-type rhBPI and NCY103 significantly (P < 0.05) decreased blood levels of LPS throughout an 8-hr evaluation period following live bacterial challenge. Two hours following E. coli administration, LPS levels peaked in the controls, at 6.86 +/- 3.22 ng/ml, whereas LPS levels were 3.39 +/- 2.1 ng/ml in the BPI group and 2.04 +/- 1.18 ng/ml in the NCY103 group. Tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 levels likewise were attenuated in the treatment groups, whereas circulating sTNFR I was significantly (P < 0.05) reduced only in the BPI group. Leukocytopenia and granulocytopenia were significantly (P < 0.02) lessened in the BPI group, by an average of 59% leukocytopenia and 65% granulocytopenia, respectively. This study supports the concept of E. coli LPS neutralization by BPI in vivo and demonstrates that a moderate (70%) reduction in peak LPS-LAL activity is sufficient to alter some hematologic and cytokine manifestations of bacteremia.
 ...
PMID:The role of bactericidal/permeability-increasing protein in the treatment of primate bacteremia and septic shock. 819 14

To study mechanisms of antibiotic effects in typhoid fever, levels of interleukin-6 (IL-6), gamma interferon (IFN-gamma), and cytokine receptors (tumor necrosis factor receptor [TNF-R] p55 and TNF-R p75) were measured in the plasma of 29 adult Nepalese with culture-positive typhoid fever before therapy and on days 4 and 15 after start of therapy with either ceftriaxone at 2 g/day for 3 days or chloramphenicol at 50 mg/kg of body weight per day for 14 days. Bacteriologic cure was defined as blood cultures testing negative on days 4 and 15 after start of therapy; clinical cure was defined as symptomatic improvement within 5 days after start of therapy and absence of relapse. Clinical and bacteriologic cures occurred in 24 patients. There were two clinical failures, two patients who failed to complete therapy because of leukopenia, and one relapse. Mean levels before therapy were elevated compared with those in healthy controls (IL-6, 11.4 pg/ml; IFN-gamma, 1.3 ng/ml; TNF-R p55, 3.8 ng/ml; and TNF-R p75, 6.1 ng/ml) and fell progressively during and after therapy. For six patients (three in each treatment group) who showed prolonged fever (> 5 days) or relapse, mean levels of IL-6 and TNF-R p55 before therapy (29.5 pg/ml and 6.1 ng/ml, respectively) and on day 4 (17.7 pg/ml and 4.0 ng/ml) were significantly greater than corresponding means for 23 patients who showed early defervescence (on admission, 6.7 pg/ml and 3.3 ng/ml, and on day 4, 1.8 pg/ml and 2.7 ng/ml, P < .05). These results indicate that the concentrations of plasma cytokines and their receptors are elevated in typhoid fever and that these concentrations can be useful in predicting outcome.
 ...
PMID:Interleukin-6, gamma interferon, and tumor necrosis factor receptors in typhoid fever related to outcome of antimicrobial therapy. 828 27

FR167653 (1-[7-(4-fluorophenyl)-1,2,3,4-tetrahydro-8-(4-pyridyl)pyrazolo[5-1-c] [1,2,4]triazin-2-yl]-2-phenylethanedione sulfate monohydrate) is a low molecular weight inflammatory cytokine inhibitor that inhibits the production of interleukin-1 alpha, interleukin-1 beta and tumor necrosis factor-alpha (TNF-alpha) in human monocytes stimulated with lipopolysaccharide, and in human lymphocytes stimulated with phytohemagglutinin-M. FR167653 inhibited these cytokines in a dose-dependent manner (IC50 values were 0.84, 0.088, 1.1 microM and 0.072, respectively). However, FR167653 did not inhibit even at 10 microM interleukin-6 production by human monocytes, and the production of interleukin-2 and interferon-gamma by human lymphocytes. We evaluated the effect of FR167653 on lipopolysaccharide-induced disseminated intravascular coagulation in rats. FR167653 (0.032-0.32 mg/kg/h for 4 h, intravenous infusion) markedly improved thrombocytopenia and plasma coagulation parameters in a dose-dependent manner, but not leukopenia in this mode. Plasma interleukin-1 and TNF-alpha levels were elevated by lipopolysaccharide administration and the treatment with FR167653 (0.31 mg/kg/h for 4 h) inhibited the increased plasma interleukin-1 (100.0%) and plasma TNF-alpha (89.2%) levels. These results suggest that interleukin-1 and TNF-alpha may play a pivotal role in the pathogenesis of DIC. FR167653 can act as a protective drug in lipopolysaccharide-induced DIC, and this protection is due to an inhibition of increased plasma interleukin-1 and TNF-alpha.
 ...
PMID:Effect of FR167653, a cytokine suppressive agent, on endotoxin-induced disseminated intravascular coagulation. 895 29

There is a need for more insight into the pathogenesis of Streptococcus pneumoniae pneumonia, as the fatality rate associated with this disease remains high despite appropriate antibiotherapy. The host response to pneumococci was investigated after intranasal inoculation of CD1 mice with 10(7) log-phase CFU of bacteria. We identified five major pathogenesis steps from initial infection to death. In step 1 (0 to 4 h), there was ineffective phagocytosis by alveolar macrophages, with concurrent release of tumor necrosis factor alpha (TNF), interleukin-6 (IL-6), and nitric oxide (NO) in bronchoalveolar lavage (BAL) fluid, TNF, IL-6, and interleukin-1 alpha (IL-1) in lung tissues, and IL-6 in serum, which were associated with tachypnea and hemoconcentration. In step 2 (4 to 24 h), bacterial growth in alveoli and polymorphonuclear cell recruitment from bloodstream to lung tissue (high myeloperoxidase levels) to alveoli were associated with high release of all three cytokines and leukotriene B4 (LTB4) in tissue and BAL fluid, as well as transient spillover of IL-1 in serum. In step 3 (24 to 48 h), despite downregulation of TNF and IL-1 in BAL fluid and lungs, there was appearance of injury to alveolar ultrastructure, edema to interstitium, and increase in lung weight as well as regeneration of type II pneumocytes and increased secretion of surfactant; bacteria progressed from alveoli to tissue to blood, and body weight loss occurred. In step 4 (48 to 72 h), strong monocyte recruitment from blood to alveoli was associated with high NO release in tissue and BAL fluid, but there was also noticeable lymphocyte recruitment and leukopenia; bacteremia was associated with TNF and IL-6 release in blood and thrombocytopenia. In step 5 (72 to 96 h), severe airspace disorganization, lipid peroxidation (high malondialdehyde release in BAL fluid), and diffuse tissue damage coincided with high NO levels; there was further increase in lung weight and bacterial growth, loss in body weight, and high mortality rate. Delineation of the sequential steps that contribute to the pathogenesis of pneumococcal pneumonia may generate markers of evolution of disease and lead to better targeted intervention.
 ...
PMID:Cytokine kinetics and other host factors in response to pneumococcal pulmonary infection in mice. 948 75

Oncostatin M (OM) is a member of the interleukin-6 (IL-6) cytokine subfamily. The binding of OM to its receptor initiates signal transduction through JAK-signal transducers and activators of transcription (STAT) pathways and activates transcription activators through mitogen-activated protein (MAP) kinases. Results of in vitro assays documented that OM modulates cytokine expression and alters the production of proteases that down-regulate inflammation. Administration of OM to lipopolysaccharide (LPS)-challenged mice lowered serum tumor necrosis factor-alpha (TNF-alpha) levels and decreased the lethal effects of LPS administration. OM also reduced inflammation in animal models of human disease, including inflammatory bowel disease, antibody-induced arthritis, and experimental autoimmune encephalomyelitis. Preclinical safety studies have been conducted in the mouse and monkey. Mice were administered OM (subcutaneously) at 72, 360, or 1,560 micrograms/kg/day in a 2-wk toxicity study. Decreased body weights occurred at 1,560 micrograms/kg. Drug-related changes at 360 and 1,560 micrograms/kg consisted of dermal irritation at the injection site, leukopenia, and thymic lymphoid depletion; all changes were reversible following a 2-wk recovery period. In a 2-wk subcutaneous study in monkeys, OM was administered at 1, 5, 15, 45, or 150 micrograms/kg/day. At all doses there was reversible, transient inappetence and dermal irritation at the injection site. Drug-related changes at 5, 15, 45, and 150 micrograms/kg consisted of reversible elevations in both serum amyloid A and IL-6, and reversible thymic lymphoid depletion. Transient increases in body temperature occurred at 15, 45, and 150 micrograms/kg. The observed spectrum of immunomodulatory effects suggests that OM may have therapeutic utility in treating chronic inflammatory diseases.
 ...
PMID:Oncostatin M: development of a pleiotropic cytokine. 1020 78

The myelodysplastic syndromes (MDS) are a heterogenous family of hematologic disorders characterized by ineffective hematopoiesis. Because of the variability between patients regarding prognosis and morbidity related to the disease, consensus regarding the management of these patients has been difficult. Over the past several years, new prognostic scoring systems such as the International Prognostic Scoring System (IPSS) have attempted to provide a projection for long-term stability of the percentage of patients who have "low-grade" or indolent MDS. Unfortunately, its lack of prospective use in clinical trials and other settings has thus far failed to validate it as a functional decision-making tool. Thus, investigators have hypothesized that separating patients based on more simplistic treatment-oriented guidelines may be more efficient. For the majority of patients with MDS, no curative option exists. Patients who are young enough and have an available matched sibling or matched unrelated donor may undergo an allogeneic bone marrow transplant (BMT) with a potential cure rate of 30% to 50%. The major issue regarding this approach is the relatively high morbidity and the risk that the patient's lives may be shortened, that their quality of life will be worsened, or that no overall benefit will occur (relapse). Compounding the issue of selection and timing for BMT is the fact that the best results in terms of relapse-free survival appear to be in the subset of patients with early or low-grade MDS, characterized by refractory anemia with or without ringed sideroblasts. For these patients, lacking a donor for BMT, the major issue has become the consideration of induction chemotherapy. While dose-intensive chemotherapy may improve outcome in a small percentage of patients, the majority of elderly patients with MDS are not optimal candidates for such an approach. As a result, supportive care has a major role for patients with MDS and depending on the French-American-British (FAB) presentation and comorbid illnesses may be the preferred approach. Erythropoietin, a growth factor, is perhaps the most commonly used supportive care after transfusion. The use of colony-stimulating growth factors to support leukopenia is currently under investigation. The use of thrombopoietic agents has lagged behind in the management of MDS patients. Investigation of interleukin-6 (IL-6), a thrombopoietic cytokine, showed some ability to increase platelets through significant toxicity. Investigation of IL-11, an approved thrombopoietic growth factor, is preparing to start and should aid in determining its role in this setting.
 ...
PMID:Advances in supportive care of myelodysplastic syndromes. 1053 Jul 13


1 2 3 Next >>