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)

Endothelin is produced by injured or ischemic endothelium and causes monocyte production of interleukins-6 and 8 in vitro. Endothelin levels increase in patients with burn injuries, and we asked whether interleukin-6 and 8 levels increased in patients with burn injuries concurrently with endothelin. Fourteen patients with more than 20% body surface area burns were resuscitated to maintain urine output of 0.5 to 1.0 ml/kg/hr. Blood was drawn on admission and at 12, 24, and 48 hours. Endothelin was measured by radioimmunoassay, interleukins-6 and 8 were measured by enzyme-linked immunosorbent assay. Endothelin levels increased to 6.1 +/- 2.3 fmol on admission, 5.7 +/- 2.1 at 12 hours, 6.9 +/- 2.7 at 24 hours, and 6.4 +/- 2.7 at 48 hours (vs 0.5 in healthy controls). Interleukin-6 increased to 243 +/- 220 pg/ml on admission, 276 +/- 198 at 12 hours, 400 +/- 282 at 24 hours, and 379 +/- 274 at 48 hours (vs less than 50 in healthy controls). Interleukin-8 increased to 504 +/- 309 pg/ml on admission, 483 +/- 263 at 12 hours, 575 +/- 306 at 24 hours, and 698 +/- 667 at 48 hours (vs less than 50 in controls). Endothelin-1 and interleukin-6 and 8 levels increase in patients with burn injuries. Endothelin-mediated activation of monocytes that cause cytokine production may have clinical relevance in patients with burn injuries.
 ...
PMID:Endothelin-1, interleukin-6, and interleukin-8 levels increase in patients with burns. 888 60

The study attempts to evaluate the role of interleukin-6 (IL-6) in the pathogenesis of chronic hepatitis. We have used EIA sensitive methods to determine the serum concentration in patients with chronic active hepatitis of HB (+) (CAH-HE Ag+) antigen, with chronic active hepatitis of HB(-) (CAH-HBAg-) antigen and in those with persistent chronic hepatitis of HB(+) (CPH-HBAg+) antigen, compared with a group of controls (blood donors) in whom HBAgs, antiHBs, HBAge, antiHBe and anti HBc were absent. Disease status diagnosis was given in accordance with international conventions, immunologic tests included. The fact that the T lymphocytes with a CD56 are present in the liver and that same marker is also encountered on the Kuppfer cells, but not on the T lymphocytes in circulation, shows that in the liver the interleukin 6 is produced by the activated T lymphocytes and by the Kuppfer cells. Therefore, in such conditions, LB stimulation and growth is performed rather by IL-6 and to a lesser extent by IL-8. This statement is also supported by the finding that in the lymphocyte cultures in the peripheral blood there is no difference in the response to polyclonal mitogens between patients with CAH-HBAg(+) and those with CAH-HBAg(-). Also, there are no significant differences in the total immunoglobulin concentrations, but there are differences in the IgM concentration (greater in CAH-HBAg(+). In our investigations, the serum level of IL-6 (40.1 +/- 6.8 pg/ml) was higher in those with higher immunoglobulin concentrations-both IgG, but more particularly IgM. The IgM increase was correlated with the presence of HBAg. Therefore, the highest IL-6 values were found in CAH with HBAg(+). Increases of serum IL-6 concentrations were found during intervals of severe hepatic aggression manifested in a cytolitic syndrome, with transaminase increase. In the case of determinations in dynamics, the values decreased as the enzyme titre decreased. We can state that the serum activity of IL-6 reflects the degree of liver inflammation and can be used as a parameter for monitoring the disease.
 ...
PMID:Immune mechanisms in the process of hepatopathies chronicization. Contribution and role of lymphokines. 889 81

Endothelial cells (EC) play a key role in the inflammatory response, both by the production of proinflammatory cytokines and by their interaction with leukocytes. Molecular genetic analysis has demonstrated that functional NF-kappa B sites are involved in the transcription of interleukin-6 (IL-6), IL-8, and granulocyte-macrophage colony-stimulating factor (GM-CSF) genes in response to inflammatory mediators. Thus, we have explored the effect of two inhibitors of the NF-kappa B activation, pyrrolidine dithiocarbamate (PDTC) and N-acetylcysteine (NAC), on the production of these cytokines by EC. Both PDTC and NAC inhibited, in a dose-dependent manner, the synthesis of IL-6, IL-8, and GM-CSF induced by tumor necrosis factor (TNF)-alpha or bacterial lipopolysaccharides (LPS) in human umbilical vein endothelial cells (HUVEC). PDTC appeared to prevent IL-6, IL-8, and GM-CSF gene transcription, as it blocked the induction of specific mRNA by TNF-alpha or LPS. The TNF-alpha mediated transcriptional activation of a chloramphenicol acetyltransferase (CAT) plasmid containing three copies of the -72 kappa B binding site from the IL-6 promoter was abrogated by PDTC. According to transfection experiments, electrophoretic mobility shift assays (EMSA) demonstrated that the antioxidant prevented the induction of NF-kappa B DNA-binding activity by TNF-alpha. Under the same conditions, PDTC by itself or in combination with TNF-alpha, enhanced the DNA-binding activity of AP-1, as well as c-fos and c-jun mRNA levels. Altogether, these results indicate that the antioxidant PDTC specifically inhibits the transcription of IL-6, IL-8, and GM-CSF genes through the inhibition of the NF-kappa B activation, while increasing the expression of AP-1. Our data make evident the antiinflammatory and immunoregulatory potential of the pharmacological inhibition of the NF-kappa B activation. In addition, PDTC and related molecules may be a useful tool to explore the expression of genes involved in the inflammatory response.
 ...
PMID:Pyrrolidine dithiocarbamate inhibits the production of interleukin-6, interleukin-8, and granulocyte-macrophage colony-stimulating factor by human endothelial cells in response to inflammatory mediators: modulation of NF-kappa B and AP-1 transcription factors activity. 889 14

Biologic dressings are believed to stimulate wound healing in a variety of wound types. Cryopreserved allograft skin (CAS) is used as a biologic dressing for excised wounds, partial-thickness wounds, and meshed split-thickness skin grafts, and the use of allogenic or autologous cultured epithelial sheets (CES) has been reported to enhance healing of skin ulcers and deep partial-thickness wounds. However, limitations of allograft skin include bacteriologic and viral safety, limited availability, cost, and ease of handling. Previously we have reported the successful use of human keratinocytes cultured to single-layer confluence on Hydroderm polyurethane membranes (HD/HK) for grafting of full-thickness wounds. In this study we evaluated the release of five different growth peptides (transforming growth factors alpha and beta (TGF-alpha, TGF-beta), interleukin-6, interleukin-8, and melanoma growth stimulatory activity from CAS, CES, and HD/HK grafts. Highest levels of TGF-alpha were found for HD/HK (728 +/- 115 pg/10 cm2 of membrane) followed by CES (491 +/- 137 pg/10 cm2; NS). No TGF-alpha was detectable for CAS, and 3.7-fold, and 25-fold higher levels of interleukin-6 were found for CES (257 +/- 12.7 U/10 cm2) compared with HD/HK and CAS, respectively. Interleukin-8 had similar levels for CES (0.65 +/- 0.7 ng/10 cm2) and HD/HK (0.88 +/- 0.12 ng/10 cm2), whereas melanoma growth stimulatory activity was elevated in CES (2314 +/- 97 pg/10 cm2) compared with HD/HK (1071 +/- 55 pg/10 cm2). TGF-beta was barely detectable for CES and HD/HK. Cryopreserved allograft showed high levels of TGF-beta (5.2 +/- 1.6 ng/10 cm2). Overall mitogenic activity of the supernatants on keratinocyte cultures was assessed. Highest proliferation was seen for CES supernatants followed by HD/HK (NS). Supernatants from CAS had an antiproliferative effect on keratinocytes. We conclude that a single layer of keratinocytes cultured on a polyurethane membrane facilitates keratinocyte proliferation similar to CES, whereas cryopreserved allograft has no mitogenic effect on keratinocytes.
 ...
PMID:Growth peptide release from biologic dressings: a comparison. 895 39

We examined the biological function of a nonstructural regulatory protein, NS1, of human parvovirus B19. Because of the cytotoxic activity of NS1, human hematopoietic cell lines, K562, Raji, and THP-1, were established as transfectants which produce the viral NS1 protein upon induction by using bacterial lactose repressor/operator system. NS1 was significantly produced in the three transfectant cells in an inducer dose- and time-dependent manner. Surprisingly, these three transfectants secreted an inflammatory cytokine, interleukin-6 (IL-6), in response to induction. However, no production of other related cytokines, IL-1beta, IL-8, or tumor necrosis factor alpha, was seen. Moreover, NS1-primed IL-6 induction was transiently demonstrated in primary human endothelial cells. Analysis with luciferase reporter plasmids carrying IL-6 promoter mutant fragments demonstrated that NS1 effect is mediated by a NF-kappaB binding site in the IL-6 promoter region, strongly implying that NS1 functions as a trans-acting transcriptional activator on the IL-6 promoter. Our novel finding, IL-6 induction by NS1, supports the possible relationship between parvovirus B19 infection and polyclonal activation of B cells in rheumatoid arthritis and indicates that NS1 protein may play a significant role in the pathogenesis of some B19-associated diseases by modulating the expression of host cellular genes.
 ...
PMID:A cytotoxic nonstructural protein, NS1, of human parvovirus B19 induces activation of interleukin-6 gene expression. 897 Sep 71

The beneficial effects of glutamine on immune function in vitro have been well described. Severely ill surgical patients undergo glutamine depletion and this has been implicated as a cause of immune dysfunction in vivo. With the introduction of the stable dipeptides of glutamine into total parenteral nutrition (TPN) regimens, the clinical effects of glutamine on the immune system have taken on an increased relevance and importance. In a randomized clinical trial, we have shown that glutamine-supplemented TPN increased the T cell mitogenic response in patients undergoing colorectal resection. This was not associated with an altered production of the pro-inflammatory cytokines interleukin-6 (IL-6) or tumor necrosis factor (TNF). In a subsequent clinical trial comparing glutamine-supplemented TPN with control TPN in patients with severe acute pancreatitis there was a similar modest enhancement of the T cell response in the glutamine-supplemented group. Although Il-6 and TNF production were again unchanged, there was a significant reduction in IL-8 production in the glutamine-supplemented group. Glutamine may exert its immunological effects by a direct action on the cells of the immune system. Possible indirect mechanisms by which glutamine may influence the immune system include the maintenance of gut barrier function, or the preservation of action of the antioxidant glutathione.
 ...
PMID:Effect of glutamine on immune function in the surgical patient. 897 26

To characterize the kinetics of grain dust-induced airflow obstruction and inflammation in the lower respiratory tract, we performed serial spirometry and bronchoalveolar lavage (BAL) in human subjects and whole-lung lavage in mice following a single inhalation exposure to comparable dosages of corn dust extract (CDE). Following inhalation of CDE, our human study subjects developed significant airflow obstruction 10 min postexposure which persisted for 48 h. Human subjects and mice had similar acute and persistent changes in lavage cellularity after exposure to CDE. A profound increase in the concentration of lavage neutrophils was present in the initial postexposure lavage in both human subjects and mice. This increase persisted for 96 h in human subjects and 48 h in mice. Small but significant increases in lavage macrophage concentration were present 48 h postexposure in human subjects and at 96 h postexposure in mice. Inhalation of CDE resulted in a significant increase in the concentration of proinflammatory cytokines tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) in the lavage fluid of both human subjects and mice. Similarly, significant increases in lavage concentrations of IL-8 in humans and macrophage inflammatory protein-2 (MIP-2) in mice occurred after inhalation of CDE. The lavage concentration of all measured proinflammatory cytokines returned to baseline levels by 168 h in humans and 96 h in mice. These findings suggest that a single inhalation challenge of CDE results in airflow obstruction and lower respiratory tract inflammation that may last for several days. These physiologic and inflammatory responses appear to be self-limited with no evidence of persistent injury 1 wk after the inhalation challenge. Moreover, the inflammatory response in the lower respiratory tract after inhalation of grain dust is similar in human subjects and mice, suggesting that the mouse may be an appropriate model for further investigation of grain dust-induced inflammation.
 ...
PMID:The kinetics of grain dust-induced inflammation of the lower respiratory tract. 900 21

The objective of the present study was to investigate the effects of isolated limb perfusion (ILP) with tumour necrosis factor alpha (TNF-alpha) and melphalan in patients with cancer on, first, plasma levels of cytokines, second, systemic monocyte and T-lymphocyte distribution and, third, the ability of mononuclear cells to produce cytokines upon stimulation in vitro. Six patients undergoing an ILP were entered into the study (group 1). In addition, patients undergoing a major surgical operation (group 2) minor operation (group 3) as well as healthy volunteers (group 4) were included as control groups. Sensitive enzyme-linked immunosorbent assays (ELISAs) were used to measure TNF-alpha and interleukin-6 (IL-6) plasma levels at various time points during and after operation. Furthermore, the percentage of monocytes and T lymphocytes was determined in all studied groups using a FACScan. In addition, cytokine production upon stimulation with lipopolysaccharide (LPS) and a combination of anti-CD3/anti-CD28 monoclonal antibodies in whole-blood cultures was investigated. Increased plasma levels of TNF-alpha and IL-6 in patients undergoing ILP was observed, but only IL-6 appeared to be increased in patients treated with a major operation. No significant fluctuations were found in the other groups studied. Concerning the number of monocytes, a significant decrease was observed only in patients treated with ILP. Furthermore, a decreased production of TNF-alpha, IL-6 and IL-8 upon various types of stimulation in vitro was found in those patients, but also after a major operation. In conclusion, the results of the present study show increased plasma levels of cytokines in patients treated with ILP and major operation. Furthermore, a decrease in numbers of monocytes in the circulation and the ability of mononuclear cells to produce cytokines in vitro may be induced by administration of TNF-alpha in ILP. Although similar results were found in patients treated with major operation, the underlying mechanisms of this phenomenon remain to be elucidated.
 ...
PMID:Effects of isolated limb perfusion with tumour necrosis factor-alpha on the function of monocytes and T lymphocytes in patients with cancer. 901 83

The microvascular endothelial cell (MVEC) is a major target of inflammatory cytokines overproduced in conditions such as sepsis and infectious diseases. We addressed the direct and indirect effects of tumor necrosis factor (TNF) on endothelial cells that can be relevant for the pathogenesis of septic shock, with particular attention to the acute respiratory distress syndrome (ARDS) and to cerebral malaria (CM). To identify functional and phenotypical changes occurring in MVEC during sepsis, we isolated these cells from the lungs of patients who died of ARDS. The constitutive expression of ICAM-1 and, to a lesser extent, VCAM-1, CD14, and TNFR2 were significantly increased on MVEC isolated from ARDS patients compared with control MVEC, whereas ELAM-1 and TNFR1 were not increased. We found that lung MVEC from ARDS patients present a procoagulant profile and a higher production capacity of interleukin-6 (IL-6) and IL-8 when compared with those from controls. As in pulmonary MVEC derived from ARDS patients, the only TNFR type found up-regulated in brain microvessels during CM was TNFR2. This increase in TNFR2 expression only occurred in CM-susceptible mice at the onset of the neurological syndrome. We therefore investigated the role of TNFR2 in the development of this brain pathology by comparing the incidence of CM in wild-type and TNF receptor knock-out mice. Unexpectedly, the genetic deficiency in TNFR2, but not in TNFR1, conferred protection against CM and its associated mortality. No ICAM-1 up-regulation was detected in the brain of Tnfr2 knockout mice, indicating a close correlation between protection against CM-associated brain damage, absence of TNFR2, and absence of ICAM-1 up-regulation in the brain. Our results in ARDS and CM indicate a specific up-regulation of TNFR2, but not of TNFR1, on lung and brain MVEC, respectively. This increased expression leads to a reduced sensitivity toward TNFR1-mediated phenomena, such as the sensitized TNF cytolytic activity on lung MVEC. In contrast, the sensitivity toward TNFR2-mediated effects, such as ICAM-1 induction by membrane-bound TNF, is increased on brain and lung MVEC expressing increased levels of TNFR2. Therefore, the ICAM-1-inducing effect, rather than the direct cytotoxicity of inflammatory cytokines, such as TNF, appears to be crucial in ARDS and CM-induced endothelial damage, and TNFR2 seems to play an important role in this activity in vivo.
 ...
PMID:TNF receptors in the microvascular pathology of acute respiratory distress syndrome and cerebral malaria. 912 3

Bronchial epithelial cells play an important role in the pathogenesis of some inflammatory diseases of bronchial mucosa. Epithelial-cell-derived cytokines are important in the elucidation of the mechanism by which airway inflammation occurs, especially in respiratory virus infection, because these cells are the primary sites of viral infection. We infected bronchial epithelial cells, NCI-H292, with influenza virus A (H3N2) and examined the concentrations of cytokines, interleukin-6 (IL-6), IL-8 and regulated on activation, normal T cells, expressed and secreted (RANTES), in the culture media of infected cells using the enzyme-linked immunosorbent assay system and gene expression of RANTES on epithelial cells by the reverse-transcriptase-polymerase chain reaction method. We found that significant amounts of IL-6, IL-8 and RANTES were released. RANTES mRNA was also detected in infected bronchial epithelial cells. It is suggested that cytokine production in human bronchial epithelial cells may contribute to the pathogenesis of airway inflammatory disorders.
 ...
PMID:Expression of cytokines on human bronchial epithelial cells induced by influenza virus A. 913 May 60


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>