Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Surgery leads to significant modulation of the immune system, in which cytokines play a major role. Circulating interleukin 6 (IL-6) and IL-1 have been reported following surgery whereas tumor necrosis factor alpha (TNF-alpha) is only found in gut ischemia-associated surgery. We have investigated the consequences of surgery on in-vitro cytokine production by human monocytes stimulated by lipopolysaccharide (LPS) and staphylococcal toxic shock syndrome toxin-1 (TSST-1). Comparisons were made between the responsiveness of cells obtained the day before (D-1), during (D0) and after (D1, D2, D3) surgery. Patients undergoing abdominal aortic surgery (N = 9), carotid surgery (N = 4) and spinal surgery (N = 4) have been studied. A significant decrease of TNF-alpha, IL-1 beta and IL-1 alpha production by monocytes prepared from blood samples taken during the surgery was noticed, whereas IL-6 production was not significantly modified. On D2 a significant increase of monocyte responsiveness was observed and levels of cytokine productions rose back to initial values by the end of the follow up. The diminished in-vitro cytokine production observed during surgery might be the consequence of the effects of anaesthetic drugs, whereas the enhancement observed on D2 might reflect the surgical stress, leading to in-vivo priming of circulating monocytes.
Cytokine 1992 Nov
PMID:Influence of surgery on in-vitro cytokine production by human monocytes. 129 41

We studied the ex vivo secretion of tumor necrosis factor (TNF) and interleukin 2 (IL-2) by splenocytes after circulatory shock induced by intestinal ischemia and reperfusion in rats. Shock was induced by total occlusion of the superior mesenteric artery followed by reperfusion. In a second group, vascular occlusion was maintained throughout the experimental protocol. A third group of sham rats and a fourth group of control rats with a negligible surgical procedure were also studied. "Spontaneous" (untriggered) secretion of TNF by splenocytes was higher in the ischemia-reperfusion group than in all other groups (p < 0.01), but did not increase significantly after stimulation with LPS. Splenocytes from control rats exhibited a marked increase in TNF secretion after stimulation with LPS to values similar to those in the ischemia-reperfusion group. A diminished, though statistically significant increase in LPS-stimulated secretion of TNF was detected in the sham and ischemia only groups of rats (p < 0.05) from untriggered values in each. Untriggered secretion of IL-2 was similar in all groups. However, when compared to control rats, splenocytes from the three surgically manipulated groups exhibited suppressed secretion of IL-2 in response to stimulation with Con A (p < 0.05). These results support the role played by TNF in mediation of shock and point to spleen macrophages as a source of TNF after intestinal ischemia and reperfusion. Our results also demonstrated postinjury alteration in immune function manifested by depressed ability of splenocytes to increase the production of IL-2 after stimulation with Con A.
Lymphokine Cytokine Res 1992 Oct
PMID:Ex vivo secretion of tumor necrosis factor and interleukin-2 by rat splenocytes after intestinal ischemia and shock. 146 63

Cytokine induction of intercellular adhesion molecule-1 (ICAM-1) in cardiac myocytes may be a critical step in inflammation associated with ischemia-reperfusion injury. We investigated the involvement of tumor necrosis factor-alpha (TNF-alpha), interleukin 6 (IL-6), and interleukin 8 (IL-8) on neutrophil-myocyte adhesion; These cytokines are increased in plasma of patients with acute myocardial infarction (AMI). ICAM-1 expression on cultured neonatal rat cardiac myocytes was determined through immunohistochemical and enzyme-linked immunosorbent assay (ELISA) analysis. ICAM-1 mRNA expression in myocytes was investigated by Northern blot hybridization. Rat neutrophils isolated from peripheral blood (PB) were used for adherence assay. In immunohistochemical study, cultured neonatal rat cardiac myocytes constitutively expressed ICAM-1 molecules. In ELISA analysis, ICAM-1 molecule expression on myocytes was significantly stimulated by TNF-alpha (100 U/ml), but not by IL-6 (100 U/ml) or IL-8 (100 ng/ml) dose dependently. The effect of TNF-alpha was observed as early as 6 h after stimulation. Levels of ICAM-1 mRNA were very low or almost undetectable in unstimulated myocytes, but its expression was markedly induced after exposure to TNF-alpha for 3 h. IL-6 and IL-8 showed no effect on ICAM-1 mRNA accumulation. Adhesion of rat neutrophils to myocytes was stimulated by TNF-alpha, and the effect of TNF-alpha on adherence was significantly inhibited by an anti-ICAM-1 monoclonal antibody (MoAb). These results show that TNF-alpha, but not IL-6 and IL-8, promotes neutrophil-myocyte adhesion through ICAM-1 expression, suggesting involvement of TNF-alpha in inflammation associated with ischemia-reperfusion injury.
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PMID:Neutrophil adherence to rat cardiac myocyte by proinflammatory cytokines. 751 17

The myocardial ischemia and reperfusion injury is caused by the re-introduction of coronary circulation in ischemic myocardial tissues. A number of experiments demonstrate that immunological response such as adherence of neutrophils to endothelial cells play a critical role in reperfusion injury. In this paper, the effect of global ischemia and reperfusion on the expression of cytokine genes by myocardial tissues as well as cell adhesion molecules by neutrophils were studied by using Langendorff model. Cardiac dysfunction and immunological response in 25 min global ischemia at 37.5 degrees C followed by 60 min reperfusion were studied in isolated rat heart perfused with blood supplied from support rat (Langendorff model). Cardiac functions were measured with a left intraventricular balloon. The mean post-experimental reduction of the left ventricular end-systolic pressure were 87.5 +/- 1.6% of pre-experimental level in the control perfusion group and 55.5 +/- 5.8% in the reperfusion group. Immunofluorescence flow cytometry showed that ischemia and reperfusion injury did not affect the expression of adhesion molecules on neutrophils which were isolated from perfused blood samples. Cytokine gene expression was analyzed by direct analysis of mRNA obtained from the blood-perfused, isolated rat heart. The level of expression of the cytokine genes was assessed using semiquantitative reverse transcriptase-polymerase chain reaction (semiquantitative RT-PCR). IL-6, IL-8, IFN-gamma, TNF-alpha were expressed in normal heart tissue at low level and were upregulated following ischemia and reperfusion. IL-1 beta, MCP-1 and IL-1 receptor antagonist were not expressed at detectable level in normal heart but were induced following global ischemia. IL-1 alpha was not expressed at detectable level in normal heart but was induced following reperfusion of the ischemic heart. Histological examination of myocardial tissue from the reperfusion group revealed no evidence of myocardial necrosis. Only a mild interstitial edema as well as weak focal hemorrhage was detected after reperfusion of ischemic hearts. These results suggest that there is a process which causes early stage of post-ischemic myocardial dysfunction without involving myocardial necrosis nor infiltration of inflammatory cells.
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PMID:[Cardiac dysfunction and endogenous cytokines in global ischemia and reperfusion injury]. 811 7

Cytokine-induced neutrophil chemoattractant (CINC), originally identified as a chemoattractant in rat kidney epithelial cells, is related to human 'gro' and murine 'KC'. The proteins encoded by these genes belong to the chemokine alpha superfamily, most of which have neutrophil chemotactic activity. Since brain chemokines may play a significant role in neutrophil accumulation in cerebral ischemia which can contribute to the extent of tissue injury in stroke, we examined the expression of CINC mRNA in the cerebral cortex of rats subjected to focal cerebral ischemia induced by middle cerebral artery occlusion (MCAO). Significant CINC mRNA expression was observed in the ipsilateral (ischemic) cortex from 6 h (17.3 +/- 3.7%, n = 6, P < 0.05) to 24 h (32.1 +/- 3.7%, n = 5, P < 0.01) with a peak at 12 h (43.9 +/- 3.7%, n = 6, P < 0.01) after MCAO. Five days post-MCAO, CINC mRNA levels were no longer elevated. No significant CINC mRNA expression was observed in the contralateral (control) cortex. These studies suggest that message for the neutrophil chemoattractant CINC is induced early in brain tissue subjected to ischemia, and therefore supports the possibility that brain-derived chemokines support the infiltration of circulating inflammatory cells following focal stroke.
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PMID:Cytokine-induced neutrophil chemoattractant mRNA expressed in cerebral ischemia. 815 86

Cytokines are released in the central nervous system following brain injury and disease. Several of those conditions are thought to involve the accumulation of extracellular glutamate at excitotoxic concentrations, and may involve compromised glial glutamate uptake. Using primary cultures of postnatal rat hippocampus, we studied the effect of three cytokines on astrocytic high-affinity glutamate uptake. After 24 hours incubation with either tumor necrosis factors alpha (TNF-alpha), interferon gamma (IFN-gamma) or interleukin-1 beta (IL-1 beta), astrocytic glutamate uptake was markedly attenuated in a dose-dependent manner. Cytokine effects were reversed by inhibition of nitric oxide synthase (NOS) using N omega-nitro-L-arginine (LNA), NG-monomethyl-L-arginine acetate (L-NMMA) or N omega-nitro-L-arginine methyl ester (LNAME). Moreover, application of the NO donors 3-morpholinosydnonimine (SIN-1) and s-nitroso-n-acetylpenicillamine (SNAP) mimicked cytokine inhibition of glutamate uptake. These data suggest that cytokine release can inhibit astrocytic glutamate uptake through a pathway that involves the liberation of nitric oxide. Astrocytic glutamate uptake may thus be compromised under conditions that are known to cause cytokine release such as nervous system injury, inflammation and ischemia.
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PMID:Cytokine modulation of glial glutamate uptake: a possible involvement of nitric oxide. 893 Sep 85

Leukocyte recruitment from the circulation into inflammatory tissues requires a series of soluble and cell-bound signals between the responding leukocyte and vascular endothelial barrier. Chemotactic factors are believed to be responsible for this selective adhesion and transmigration. A superfamily of small, soluble, structurally-related molecules called 'chemokines' have been identified and shown to selectively promote the rapid adhesion and chemotaxis of a variety of leukocyte subtypes both in vivo and in vitro. Chemokines are produced by almost every cell type in the body in response to a number of inflammatory signals, in particular those which activate leukocyte-endothelial cell interactions. These molecules also appear to play important roles in hematopoesis, cellular activation, and leukocyte effector functions. In addition, chemokines have been found in the tissues of a variety of disease states characterized by distinct leukocytic infiltrates, including rheumatoid arthritis, sepsis, atherosclerosis, asthma, psoriasis, ischemia/reperfusion injury, HIV replication, and a variety of pulmonary disease states. This review will primarily focus on the role of chemokines in cell adhesion and trafficking as well as their role as effector molecules.
Cytokine Growth Factor Rev 1996 Dec
PMID:Chemokine-leukocyte interactions. The voodoo that they do so well. 902 58

Experimental occlusion of a brain-supplying artery triggers tissue ischemia and subsequent inflammatory events that are initiated at the blood microvessel interface. Cytokine production and molecular adhesive events occur in the early moments following cerebral blood flow reduction, which underlie the transition from ischemic to inflammatory injury. Events both within the microvascular lumen and in the immediately surrounding tissue are involved. Cytokines, including TNF-alpha, IL-1 beta, IL-6, and PAF, are produced from the ischemic parenchyma and contribute to the endothelial cell expression of P-selectin, ICAM-1, and E-selectin. Platelet activation occurs paris passu and probably involves alpha-granule P-selectin to mediate PMN leukocyte-platelet interactions. Other integrin heterodimers are also involved in the early microvascular responses to ischemia. The response of the basal lamina and ECM is somewhat slower, entailing yet unproven mechanisms that most probably include the proteolytic processes of leukocyte transmigration. The modifications to microvascular structure are likely to affect both endothelial and astrocyte relationships, promote erythrocyte extravasation and hemorrhage, and contribute to tissue injury. Remodeling of the microvasculature, apparent in other tissues, involves a number of these processes. However, the enzymatic participants and regulating mechanisms are coming under study: the unraveling of regulatory mechanisms of adhesion receptor expression and their modulation, and the companion roles of integrins as mediators of structural integrity and intercellular signaling.
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PMID:Microvascular responses to cerebral ischemia/inflammation. 929 40

Adhesion molecules mediate inflammatory myocardial injury after ischemia/reperfusion. Cytokine release and hypoxia are features of acute ischemia that may influence expression of these molecules. Accordingly, we studied intercellular adhesion molecule (ICAM) and vascular cell adhesion molecule (VCAM) responses to cytokines and acute hypoxia in cultured myocardial cells. Northern blot analysis and immunoassay showed that the proinflammatory cytokines interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha stimulated concentration-dependent increases in ICAM and VCAM mRNA and protein. In both cardiac myocytes and fibroblasts, pretreatment with a specific inhibitor of nuclear transcription factor-kappaB (NF-kappaB) prevented cytokine induction of both molecules. We also found that inhibition of tyrosine kinase and p38/RK (stress-activated protein kinase) pathways prevented IL-1beta-induced ICAM and VCAM protein synthesis, whereas extracellular signal-regulated protein kinase (ERK1/ERK2) inhibition did not. Neither hypoxia (0% O2 for 6 hours) alone nor hypoxia/reoxygenation had any significant effect on ICAM and VCAM mRNA. However, hypoxia did enhance IL-1beta-induced ICAM mRNA expression in myocytes. As a possible mechanism of this synergistic action on CAM expression, hypoxia induced a time-dependent increase in the DNA binding activity of both NF-kappaB and activator protein-1 (AP-1), two transcription factors important for cell adhesion molecule expression. In contrast to the enhanced ICAM mRNA induced by IL-1beta during hypoxia, however, protein levels for this adhesion molecule were unchanged beyond IL-1beta-stimulated levels, suggesting posttranscriptional and/or posttranslational control mechanisms. We conclude that cytokines regulate ICAM and VCAM mRNA and protein in both cardiac myocytes and fibroblasts. Furthermore, adhesion molecule induction requires translocation of at least two transcription factors, NF-kappaB and AP-1.
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PMID:Expression and regulation of adhesion molecules in cardiac cells by cytokines: response to acute hypoxia. 952 62

The Transforming Growth Factor-betas (TGF-beta) are a group of multifunctional proteins whose cellular sites of production and action are widely distributed throughout the body, including the central nervous system (CNS). Within the CNS, various isoforms of TGF-beta are produced by both glial and neural cells. When evaluated in either cell culture or in vivo models, the various isoforms of TGF-beta have been shown to have potent effects on the proliferation, function, or survival of both neurons and all three glial cell types, astrocytes, microglia and oligodendrocytes. TGF-beta has also been shown to play a role in several forms of acute CNS pathology including ischemia, excitotoxicity and several forms of neurodegenerative diseases including multiple sclerosis, Parkinson's disease, AIDS dementia and Alzheimer's disease.
Cytokine Growth Factor Rev 1997 Dec
PMID:TGF-beta in the central nervous system: potential roles in ischemic injury and neurodegenerative diseases. 962 Jun 42


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