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)

Interleukin-6 (IL-6) induces acute-phase protein synthesis in human hepatocytes. We evaluated whether the contiguous hepatic macrophages, human Kupffer cells (HKC), produce IL-6 in response to an inflammatory stimulus. HKC were harvested from collagenase-digested normal liver biopsies and purified (greater than 95% by phagocytosis) by adherence. Following overnight culture, 5 x 10(5) HKC were repleted with fresh media with or without 2.5 micrograms/ml of endotoxin (LPS). Parallel cultures contained polymyxin-B (10 micrograms/ml) or antihuman-IL-6 antibody (4 units/ml). Timed supernatants were collected and IL-6 levels (ng/ml) measured (B9.9 proliferative bioassay). Data analysis was by the paired Student's t test. Unstimulated HKC produced negligible IL-6 levels (less than 0.150 ng/ml). Endotoxin invoked early and sustained HKC production of IL-6, which was completely (P less than 0.001) abrogated by the addition of the anti-IL-6 antibody. Polymyxin B, an LPS-inhibitor, also blocked (P less than 0.001) IL-6 production, indicating the specificity of the response to the inflammatory stimulus. This is the first evidence that HKC can produce IL-6 in response to LPS. Local intrahepatic production of IL-6 may provide a necessary paracrine signal for HKC to amplify directly neighboring hepatocyte acute-phase responses during inflammation in man.
 ...
PMID:Endotoxin stimulates interleukin-6 production by human Kupffer cells. 142 8

Lyme disease refers to the multisymptomatic illness in humans which results from infection with the tick-borne spirochete Borrelia burgdorferi. The white-footed mouse is the major reservoir for B. burgdorferi and, upon infection, certain inbred mice develop symptoms similar to those reported in human disease. Sonicated preparations of washed spirochetes were found to have potent mitogenic activity when cultured with lymphocytes from naive C57BL/6, C3H/HeJ, or BALB/c mice. The activity of the B. burgdorferi sonicate was approximately fourfold greater than that of a similarly prepared Escherichia coli sonicate. Polymyxin B efficiently inhibited the mitogenic activity of the E. coli sonicate but only slightly inhibited that of the B. burgdorferi sonicate, suggesting that a lipid A-containing lipopolysaccharide was not responsible for the B. burgdorferi activity. Kinetic analysis indicated peak proliferation at 2 to 3 days of culturing, suggesting polyclonal activation. B- and T-lymphocyte depletion experiments indicated that the major cell type responding to the B. burgdorferi mitogen was the B lymphocyte. This mitogen stimulated murine B cells not only to proliferate but also to differentiate into antibody-secreting cells, as demonstrated by the production of immunoglobulin by stimulated splenocytes. Furthermore, the sonicated preparation stimulated the B-cell tumor line CH12.LX to secrete immunoglobulin in the absence of accessory cells. B. burgdorferi also stimulated interleukin-6 production in splenocyte cultures. The observation that B. burgdorferi can stimulate activation of and immunoglobulin production by normal B lymphocytes may directly reflect on the development of arthritis associated with persistent infection by this organism.
 ...
PMID:Demonstration of a B-lymphocyte mitogen produced by the Lyme disease pathogen, Borrelia burgdorferi. 173 Apr 76

Polymyxin B (PmB), an agent often used to neutralize the effects of bacterial lipopolysaccharide (LPS), was shown to exert a dose-dependent stimulatory effect on the biosynthesis of C3, factor B, interleukin-6 (IL-6), and granulocyte-macrophage colony-stimulating factor (GM-CSF) in human monocytes. A low dose of PmB (1 to 5 micrograms/ml) efficiently suppressed the LPS-induced (1 or 100 ng/ml) production of IL-6, GM-CSF, and factor B, but not the C3 production induced by 100 ng of LPS per ml. A reduced level of GM-CSF may have contributed to the persisting high C3 concentrations and the apparent lack of LPS inhibition in the latter situation, since GM-CSF is an inhibitor of monocyte C3 biosynthesis.
 ...
PMID:Polymyxin B stimulates production of complement components and cytokines in human monocytes. 772 27

The concentration and accessibility of endotoxin can increase following antibiotic killing of gram-negative bacteria. There are indications that antibiotics may differ in this respect. We measured endotoxin levels in RPMI 1640 and tumor necrosis factor alpha (TNF-alpha) and interleukin-6 production in whole blood ex vivo after exposure of log-phase Escherichia coli to antibiotics belonging to different classes, in a final concentration of 0.5, 5, or 50 times the MIC. After 4 h of incubation at 50 times the MIC, ceftazidime and ciprofloxacin treatment resulted in levels of endotoxin, TNF-alpha, and interleukin-6 significantly higher than those of imipenem and gentamicin (P < 0.001). Similar differences in cytokine induction were measured after 8 h of incubation. At 0.5 times the MIC, the differences between the antibiotics in measured endotoxin and cytokine levels were small, with levels comparable to the levels in untreated cultures. Polymyxin B and, to a lesser degree, recombinant bactericidal/permeability-increasing protein 21 (rBPI-21) were found to be potent inhibitors of TNF-alpha release, supporting the concept that the differences between the antibiotics in cytokine production were indeed due to differences in amounts of biologically active endotoxin. The presence of serum from patients suffering from untreated sepsis decreased TNF-alpha production significantly, in a concentration-dependent manner.
 ...
PMID:Release of tumor necrosis factor alpha and interleukin 6 during antibiotic killing of Escherichia coli in whole blood: influence of antibiotic class, antibiotic concentration, and presence of septic serum. 776 3

The effects of intramuscular injections of minute amounts of polymyxin B were studied in 42 patients with endotoxemia. Plasma endotoxin was measured by means of an endotoxin-specific Endospecy test (Seikagaku Corp., Tokyo, Japan) after pretreatment of the plasma with a new perchloric acid method that we developed. The normal value of plasma endotoxin is less than 9.8 pg/mL. Polymyxin B was administered at a dose of 12,500 U every 6 hours. Plasma endotoxin rapidly decreased to the normal range in 40 of the 42 patients. Body temperature fell significantly. APACHE II scores were also significantly improved. Tumor necrosis factor-alpha and interleukin-6 (IL-6) decreased in survivors, while tending to persist in high values in patients who died. No side effects were observed in any of the patients. In conclusion, intramuscular injections of small doses of polymyxin B were useful in the treatment of endotoxemia.
 ...
PMID:Clinical effects of intramuscular administration of a small dose of polymyxin B to patients with endotoxemia. 820 33

Cytokines play a major role in the pathophysiology of septic shock. In this study, human peripheral blood monocytes were stimulated with peptidoglycan and teichoic acid, purified from a strain of Staphylococcus epidermidis. Polymyxin B (PM-B) was added to avoid the effects of possible contamination with endotoxin. Tumour necrosis factor-alpha (TNF), interleukin-1 beta (IL-1), and interleukin-6 (IL-6) in the supernates were measured by enzyme-linked immunosorbent assays. Peptidoglycan and teichoic acid induced TNF, IL-1, and IL-6 in a concentration-dependent manner. Teichoic acid was a weaker inducer than peptidoglycan, especially for IL-1. Lipopolysaccharide from an E. coli strain was used as a control, being 100-1000 times more potent than peptidoglycan and teichoic acid.
 ...
PMID:Peptidoglycan and teichoic acid from Staphylococcus epidermidis stimulate human monocytes to release tumour necrosis factor-alpha, interleukin-1 beta and interleukin-6. 827 59

Actinobacillus actinomycetemcomitans(Aa), elaborating a multiplicity of virulence factor and tissue-damaging products, is considered an etiological agent in periodontal disease. Serotype b is the most frequently isolated serotype in localized juvenile periodontitis patients, suggesting a particularly high periodontopathic potential for serotype b strains. Interleukin-6(IL-6) plays an important role in the mediation of inflammatory and immune responses as well as in the osteoclastic bone resorption. However, there is little information regarding the effect of the different serotypes of Aa on IL-6 production by human gingival fibroblasts (HGF). Therefore, the purpose of this study was to compare the ability of the three serotypes (a, b, and c) of Aa sonicates to induce the production of IL-6 by HGF. In fibroblast cultures, confluent monolayers of HGF were incubated with sonic extracts of Aa-511 (serotype a), Aa-Y4 (serotype b), and Aa-652 (serotype c) at various concentrations for 48 h at 37 degrees C in 5% CO2 and air. At the end of the culture period, supernatants were collected and analysed for IL-6 content by using EIA and bioassay. In order to compare the effects of non-lipopolysaccharide (LPS) activation of Aa sonicates on IL-6 production by HGF, we added polymyxin B in cultures with Aa sonicates to bind LPS. The results were summarized as follows. (1) All three serotypes of Aa sonicates had similar dose-dependent stimulant effects on IL-6 production by HGF, and the biological activities of IL-6 correlated with their immunoreactivities. (2) The maximum releases of IL-6 by HGF were achieved at concentrations of 10 to 100 micrograms protein/mL of Aa sonicates, and the ability of Aa-Y4 to induce the release of IL-6 was higher than that of Aa-511 and Aa-652 at these concentrations. (3) Polymyxin B (50 micrograms/mL) effectively decreased the amounts of IL-6 produced by stimulation of the HGF with 10 micrograms protein/mL of Aa sonicates. However, the polymyxin B-treated Aa-Y4 sonicate showed a higher ability to induce the release of IL-6 than the other two strains. These results indicate that Aa-Y4 (serotype b) has a higher potency to induce HGF secretion of IL-6; thus contributing to a comparatively stronger efficacy to the destruction of periodontal tissue in periodontitis.
 ...
PMID:[Interleukin-6 production by human gingival fibroblasts following stimulation with Actinobacillus actinomycetemcomitans]. 971 39

Leukocyte infiltration of cerebral vessels in cocaine-associated vasculopathy suggests that cocaine may enhance leukocyte migration. We have investigated cocaine's effects on leukocyte adhesion in human brain microvascular endothelial cell (BMVEC) cultures and monocyte migration in an in vitro blood-brain barrier (BBB) model constructed with BMVEC and astrocytes. Cocaine (10(-5) to 10(-9) M) enhanced adhesion of monocytes and neutrophils to BMVEC. In the BBB model, cocaine (10(-4) to 10(-8) M) enhanced monocyte transmigration. Cocaine increased expression of endothelial adhesion molecules, intercellular adhesion molecule-1 (ICAM-1, CD54), vascular cell adhesion molecule-1 (VCAM-1), and endothelial leukocyte adhesion molecule-1 (ELAM-1) on BMVEC. The peak effect on ICAM-1 expression was between 6 and 18 h after treatment. ICAM-1 was increased by cocaine in BMVEC, but not in human umbilical vein endothelial cells, and the enhancement was greater in a coculture of BMVEC with monocytes. ICAM-1 expression was enhanced by a transcriptional mechanism. Polymyxin B inhibited up-regulation of adhesion molecules by LPS but not by cocaine. In LPS-activated BMVEC/monocyte coculture, cocaine increased secretion of tumor necrosis factor-alpha and interleukin-6. Taken together, these findings indicate that cocaine enhances leukocyte migration across the cerebral vessel wall, in particular under inflammatory conditions, but the effects are variable in different individuals. Cocaine's effects are exerted through a cascade of augmented expression of inflammatory cytokines and endothelial adhesion molecules. These could underlie the cerebrovascular complications of cocaine abuse.
 ...
PMID:Cocaine enhances brain endothelial adhesion molecules and leukocyte migration. 1021 56

Lipopolysaccharides (LPS) are proinflammatory bacterial products implicated in the pathogenesis of gram-negative sepsis and septic shock. Polymyxin B (PMB), a cyclic, cationic peptide antibiotic, inhibits biological activities of LPS through high-affinity binding to the lipid A moiety. Small synthetic peptides have been designed to mimic the primary and secondary structures of PMB to determine structural requirements for binding and detoxification of lipid A and to assess possible therapeutic potential. The purpose of this study was to compare and contrast the endotoxin-neutralizing activities of two synthetic antiendotoxin peptides (SAEP-2 and SAEP-4), PMB, and an LPS core-specific monoclonal antibody (MAb), WN1 222-5, based on their abilities to inhibit CD14-mediated target cell uptake of fluorescein isothiocyanate (FITC)-conjugated LPS, detected by flow cytometry and confocal microscopy, and LPS-induced production of the proinflammatory cytokines, interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-alpha), as measured by bioassays. PMB and SAEP-4 produced dose-dependent inhibition of FITC-LPS uptake by CD14-transfected Chinese hamster ovary fibroblasts (CHO-CD14 cells) and by human peripheral blood mononuclear cells. The anti-LPS MAb, WN1 222-5, also blocked LPS uptake by these cells and synergized with PMB and SAEP-4. LPS-induced IL-6 release was inhibited by PMB, SAEP-4, and MAb WN1 222-5, and these inhibitory activities were additive or synergistic. LPS-induced TNF-alpha release by PBMC was also inhibited by PMB and SAEP-4 alone and in combination with anti-LPS MAb. SAEP-2, in contrast, produced comparatively minor decrements in cellular uptake of LPS and LPS-induced cytokine responses, and did so only in the absence of serum, while a nonsense peptide exerted no discernible inhibitory effect on LPS uptake or LPS-induced cytokine expression in the presence or absence of serum. Thus, PMB and SAEP-4, like the LPS-reactive MAb, WN1 222-5, block proinflammatory activities of LPS in part by preventing LPS recognition by membrane-bound CD14-expressing target cells. Differences in peptide structure, however, like those exemplified by SAEP-2 and SAEP-4, may differentially affect the endotoxin-neutralizing potency of these peptides despite similar binding activity against lipid A, reflecting possible differences in peptide solubility or peptide regulation of intracellular signal transduction.
 ...
PMID:Influence of synthetic antiendotoxin peptides on lipopolysaccharide (LPS) recognition and LPS-induced proinflammatory cytokine responses by cells expressing membrane-bound CD14. 1067 85

Orientia tsutsugamushi is a Gram-negative obligate intracellular bacterium, which causes scrub typhus. To understand the pathogenesis of scrub typhus, we have investigated the induction of tumor necrosis alpha (TNF-alpha) and interleukin-6 (IL-6) by O. tsutsugamushi in two murine macrophage cell lines. Both live and heat-killed orientia stimulated the production of cytokines in J774A.1 cells. Polymyxin B does not affect the secretion of cytokines. These together with the fact that the immature macrophage cell line, P388D1, did not produce TNF-alpha when induced by either live or heat-killed O. tsutsugamushi strongly argue against any roles of lipopolysaccharide (LPS) in cytokine production. Furthermore, the result that the cytokine responses were more brisk when macrophage cell lines had been induced by heat-killed O. tsutsugamushi than by live organisms strongly suggest that a heat-stable molecule might be responsible for the induction of cytokine production and O. tsutsugamushi might have mechanisms suppressing the production of inflammatory cytokines induced by its own heat-stable molecule.
 ...
PMID:Orientia tsutsugamushi suppresses the production of inflammatory cytokines induced by its own heat-stable component in murine macrophages. 1150 99


1 2 Next >>