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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Experimental and clinical observations indicate that the liver allograft is less immunogenic than other organ transplants and can promote immune tolerance. Because interleukin-10 recently emerged as a macrophage and T-cell-derived cytokine with potent immunosuppressive properties, we studied its production in 28 patients undergoing orthotopic liver transplantation. Plasma levels of immunoreactive interleukin-10 dramatically increased within 2 hr after liver allograft reperfusion, with peak levels ranging between 214 and 4998 pg/ml (median = 677 pg/ml). This systemic release of interleukin-10 was transient because it returned to low levels by 48 hr (range = 26 to 51 pg/ml). The higher interleukin-10 levels measured in right atrial blood as compared with portal blood indicated that interleukin-10 was most likely synthesized within the liver graft. To get insight into the cellular origin of interleukin-10, we also measured serum levels of interleukin-4 and interferon-gamma, both produced by T cells, and interleukin-8, a cytokine secreted by macrophages, in eight patients. Interleukin-4 and interferon-gamma levels remained undetectable in most of the patients, whereas interleukin-8 levels paralleled those of interleukin-10. Portal endotoxemia was probably not involved in interleukin-10 production because endotoxin levels remained low (< 20 pg/ml) before and after liver allograft reperfusion. Interleukin-10 plasma levels did not correlate either with cold ischemia time or with the occurrence of rejection episodes. We conclude that orthotopic liver transplantation is associated with a massive release of interleukin-10 and interleukin-8, most likely produced by allograft macrophages.
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PMID:Systemic release of interleukin-10 during orthotopic liver transplantation. 792 30

Cardiac surgery with cardiopulmonary bypass triggers an inflammatory response involving proinflammatory cytokines such as tumor necrosis factor-alpha, interleukin-6, and interleukin-8. To elucidate the pathophysiology of this cytokine response, we explored the possible differences in cytokine responses between patients undergoing heart transplantation and those undergoing coronary artery bypass grafting. Plasma levels of tumor necrosis factor-alpha, interleukin-6, interleukin-8, and interleukin-10 were measured in eight patients undergoing heart transplantation (mean age 44 years) and eight patients undergoing coronary artery bypass grafting (mean age 61 years). Duration of cardiopulmonary bypass and ischemic time were both longer in the heart transplantation group than in the coronary artery bypass grafting group (133 +/- 26 min vs 100 +/- 31 min, p < 0.05, and 130 +/- 47 min vs 58 +/- 21 min, p < 0.005, respectively). Samples were collected before heparin administration, at aortic crossclamping and declamping, and at 0.5, 1, 1.5, 2, 4, 12, and 24 hours after declamping. Tumor necrosis factor-alpha levels were significantly higher 30 minutes after aortic declamping in the heart transplantation group than in the coronary artery bypass grafting group (68 +/- 30 vs 18 +/- 5 pg/ml, p < 0.05). Interleukin-6 and interleukin-8 levels were also significantly higher 90 minutes after declamping in patients undergoing heart transplantation than in those undergoing coronary artery bypass grafting (310 +/- 63 vs 169 +/- 24 pg/ml, p < 0.05, and 73 +/- 17 vs 24 +/- 5 pg/ml, p < 0.01, respectively). Furthermore, interleukin-6 and interleukin-8 values 90 minutes after declamping were significantly correlated with the ischemic time (r = 0.72 and r = 0.82, respectively, both p < 0.05). Interleukin-10 levels in both groups rose to reach a peak value of around 115 pg/ml 1 hour after declamping. Patients undergoing heart transplantation exhibited a second peak of tumor necrosis factor-alpha, interleukin-8, and interleukin-10 levels 12 hours after declamping, probably related to the administration of rabbit antihuman thymocyte immunoglobulin (Thymoglobuline) 3 hours after declamping. Interleukin-6 levels decreased more significantly 12 and 24 hours after declamping in patients undergoing heart transplantation, probably related to methylprednisolone therapy. In conclusion, cardiopulmonary bypass is associated with the production of both proinflammatory and antiinflammatory cytokines. The production of proinflammatory cytokines in patients undergoing heart transplantation is higher than that in patients undergoing coronary artery bypass grafting, and this increase could be related to the longer duration of ischemia in the former group. The later course of cytokine levels after heart transplantation may be further influenced by immunosuppressive therapy.
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PMID:Human cytokine responses to cardiac transplantation and coronary artery bypass grafting. 875 37

Proinflammatory cytokines have been found to mediate part of the local and distant organ injury after ischemia and reperfusion (I/R). The anti-inflammatory cytokine interleukin-10 (IL-10) inhibits both TNF-alpha and IL-1, and we hypothesized that exogenous human IL-10 may decrease lung and soleus muscle injury after hindlimb I/R. Male Sprague-Dawley rats were randomly assigned to I/R (n = 10); I/R+IL-10 (10 micrograms i.v., n = 10), SHAM (n = 4); or SHAM+IL-10 (10 micrograms i.v., n = 4). Bilateral hindlimb ischemia was produced by tourniquet occlusion for 4 hr and all animals were sacrificed after 4 hr of reperfusion or at comparable times for the SHAMs. Soleus muscle cellular injury was determined by uptake of 99Tc pyrophosphate while soleus muscle capillary permeability, and lung capillary permeability were assessed by uptake of 125I-labeled albumin. Soleus muscle and lung neutrophil infiltration were measured with the myeloperoxidase assay. Serum samples were assessed for TNF-alpha production with the WEHI bioassay. Hindlimb I/R caused significant soleus muscle cellular injury, soleus muscle capillary injury, lung capillary injury, and lung neutrophil infiltration, Pretreatment with exogenous IL-10 significantly reduced soleus muscle capillary permeability and also reduced soleus muscle cellular injury, but not to a statistically significant degree. IL-10 administration also reduced pulmonary capillary permeability despite significantly increased lung neutrophil infiltration. Elevated TNF-alpha levels were found in 66% (4/6) rats in the I/R group versus 30% (3/10) rats in the I/R+IL-10 group. Exogenous IL-10 attenuates both local and distant organ injury after hindlimb I/R potentially independent of neutrophil infiltration.
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PMID:Exogenous human recombinant interleukin-10 attenuates hindlimb ischemia-reperfusion injury. 922 18

We investigated the cardioprotective effects of rat interleukin-10 in a murine model of myocardial ischemia-reperfusion (20 min ischemia, 24 h reperfusion). Interleukin-10 (100 microg/rat) administered 15 min prior to reperfusion, significantly (P < 0.01) attenuated myocardial injury compared to rats receiving only 0.9% saline as a vehicle, as indicated by a reduced loss of myocardial creatine kinase from the ischemic-reperfused myocardium. Cardiac myeloperoxidase activity was also significantly (P < 0.01) attenuated by interleukin-10 within the ischemic-reperfused region compared to vehicle treated rats. To further investigate the mechanism of interleukin-10 we observed the in vitro adherence of neutrophil to rat vascular endothelium. Interleukin-10 treatment significantly (P < 0.05) attenuated neutrophil adherence to rat superior mesenteric artery endothelium stimulated with interleukin-1beta. Thus, interleukin-10 demonstrated significant cardioprotective effects as evidenced by a decrease in myocardial creatine kinase loss as well as an inhibition of neutrophil accumulation within the myocardium. It appears as though interleukin-10 mediates its effects, at least in part, by inhibiting leukocyte-endothelial interactions.
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PMID:Cardioprotective effect of interleukin-10 in murine myocardial ischemia-reperfusion. 936 44

Ischemia/reperfusion injury of the liver requires the participation of proinflammatory cytokines, chemokines, and adhesion molecules, many of which are regulated by the transcription factor nuclear factor kappaB (NFkappaB). The anti-inflammatory cytokine, interleukin-10 (IL-10) affects inflammatory reactions, at least in part, through inhibitory effects on the transcription factor, NFkappaB. The objective of the current study was to determine whether IL-10 could suppress hepatic ischemia/reperfusion-induced NFkappaB activation and the ensuing inflammatory liver injury. C57BL/6 mice underwent partial hepatic ischemia and reperfusion with or without intravenous injections of recombinant murine IL-10. Hepatic NFkappaB activation was induced in a time-dependent fashion. IL-10 suppressed NFkappaB activation as well as messenger RNA expression of tumor necrosis factor-alpha (TNF-alpha) and macrophage inflammatory protein-2 (MIP-2). In addition, IL-10 reduced serum levels of TNF-alpha and MIP-2. Hepatic neutrophil recruitment, liver edema, and hepatocellular injury were all significantly reduced by IL-10. The data suggest that IL-10 protects against hepatic ischemia/reperfusion injury by suppressing NFkappaB activation and subsequent expression of proinflammatory mediators.
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PMID:Interleukin-10 suppresses hepatic ischemia/reperfusion injury in mice: implications of a central role for nuclear factor kappaB. 1038 57

Experimental studies have demonstrated that postischemic therapeutic interventions may delay rather than provide long-lasting neuroprotection. The purpose of this study was to determine whether mild hypothermia (33-34 degrees C) combined with the anti-inflammatory cytokine interleukin-10 (IL-10) would protect the CA1 hippocampus 2 months after ischemia. Rats were subjected to 12.5 min of normothermic (37 degrees C) forebrain ischemia by two-vessel occlusion followed immediately by: (a) 4 h of normothermic (37 degrees C) reperfusion (n = 5); (b) 4 h of postischemic hypothermia (33-34 degrees C) (n = 5); (c) 4 h of normothermia plus IL-10 (5 micrograms) treatment 30 min after ischemia and at 3 days (n = 5); or (d) 4 h of hypothermia plus IL-10 treatment (n = 5). Rats survived for 2 months and were perfusion fixed for quantitative histopathological assessment of CA1 hippocampus. Postischemic normothermia and hypothermia, as well as normothermia plus IL-10 treatment led to severe damage of the CA1 hippocampus. In contrast, the combined treatment of hypothermia with IL-10 treatment improved overall neuronal survival by 49% compared to normothermic ischemia (P < 0.01). These data emphasize the detrimental consequences of secondary inflammatory responses on ischemic neuronal damage after transient global ischemia. In postinjury settings where restricted durations of mild hypothermia can be induced, anti-inflammatory treatments, including IL-10, may promote chronic neuroprotection.
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PMID:Postischemic hypothermia and IL-10 treatment provide long-lasting neuroprotection of CA1 hippocampus following transient global ischemia in rats. 1041 51

Hepatic ischemia and reperfusion cause local and remote organ injury. This injury culminates from an integrated cascade of proinflammatory cytokines, chemokines, and adhesion molecules, many of which are regulated by the transcription factor nuclear factor-kappaB (NF-kappaB). The anti-inflammatory cytokine interleukin-10 (IL-10) has been shown to have inhibitory effects on NF-kappaB. The objective of the current study was to determine whether IL-10 could suppress pulmonary NF-kappaB activation and ensuing lung injury induced by hepatic ischemia-reperfusion. C57BL/6 mice underwent partial hepatic ischemia with or without intravenous administration of IL-10. Hepatic ischemia-reperfusion resulted in pulmonary NF-kappaB activation, increased mRNA expression of tumor necrosis factor-alpha (TNF-alpha), and macrophage inflammatory protein-2 (MIP-2), as well as increased pulmonary neutrophil accumulation and lung edema. Administration of IL-10 suppressed lung NF-kappaB activation, reduced TNF-alpha and MIP-2 mRNA expression, and decreased pulmonary neutrophil recruitment and lung injury. The data suggest that IL-10 protects against hepatic ischemia and reperfusion-induced lung injury by inhibiting lung NF-kappaB activation and the resulting pulmonary production of proinflammatory mediators.
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PMID:Interleukin-10 inhibits pulmonary NF-kappaB activation and lung injury induced by hepatic ischemia-reperfusion. 1056 76

Overwhelming inflammatory immune response can result in systemic inflammation and septic shock. To prevent excessive and deleterious action of proinflammatory cytokines after they have produced their initial beneficial effects, the immune system can release several anti-inflammatory mediators, including interleukin-10, interleukin-1 receptor antagonist, and soluble tumor necrosis factor receptors, thus initiating a compensatory anti-inflammatory response syndrome. However, in vivo the delicate balance between pro- and anti-inflammatory responses is additionally controlled by the central nervous system. Therefore, proinflammatory cytokines stimulate the hypothalamic-pituitary-adrenal axis and enhance sympathetic nerve system activity. The mediators of these neuroimmune pathways can again suppress immune cell functions to control systemic inflammation. The question is, however, what happens if the immunoinhibitory CNS pathways are activated without systemic inflammation? This can result from production of cytokines in the brain following infection, injury, or ischemia or in response to various stressors (e.g., life events, depression, anxiety) or directly from brainstem irritation. The answer is that this may generate a brain-mediated immunodepression. Many animal and clinical studies have demonstrated a stress and brain cytokine mediated decrease in the cellular immune response at the lymphocyte level. More recently, the importance of monocytes in systemic immunocapacity has been shown. Monocytic inactivation with decreased capability of antigen presentation and depressed secretion of proinflammatory cytokines increases the risk of infectious complications. Interestingly, cytokines in the brain and other stressors can also generate systemic immunodepression at the monocyte level. In this scenario the catecholamine-induced release of the potent anti-inflammatory cytokine interleukin-10 is a newly discovered mechanism of the brain-mediated monocyte deactivation in addition to the "well known" immunosuppressive action of glucocorticoids. Furthermore, other neuropeptides such as alpha-melanocyte-stimulating hormone and beta-endorphin which can be released in stressful situations have also inhibitory effects on immune cells. Thus mediators of the CNS are implicated in the regulation of immune functions and may play a role in both conditioning the host's response to endogenous or exogenous stimuli and generating a "brain-mediated" immunodepression.
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PMID:Mechanisms of brain-mediated systemic anti-inflammatory syndrome causing immunodepression. 1061 37

The nuclear enzyme poly (ADP ribose) synthetase (PARS) has been shown to play an important role in the pathogenesis of various forms of ischemia or reperfusion injury and circulatory shock. Recent studies demonstrated that inhibition or genetic inactivation of PARS is beneficial in the early phase of myocardial reperfusion injury. The aim of the present study was to investigate whether inactivation of PARS influences the delayed myocardial necrosis and the production of the proinflammatory cytokine tumor necrosis factor alpha (TNFalpha), the anti-inflammatory cytokine interleukin-10 (IL-10), and the free radical nitric oxide in the late stage of myocardial reperfusion injury. The results demonstrate that genetic disruption of PARS provides marked protection against the delayed myocardial ischemia and reperfusion injury. In addition, in the absence of functional PARS, a suppression of TNFalpha, IL-10, and nitric oxide production was found. These findings provide direct evidence that PARS activation participates in the development of delayed cell injury and delayed mediator production in myocardial reperfusion injury.
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PMID:Effect of genetic disruption of poly (ADP-ribose) synthetase on delayed production of inflammatory mediators and delayed necrosis during myocardial ischemia-reperfusion injury. 1063 71

Although tumor necrosis factor-alpha has been implicated in liver injury after both warm ischemia- and cold ischemia-reperfusion, it is unclear whether reactivity of the liver to these stimuli is similar with regard to cytokine expression. Here we compare the effects of warm and cold ischemia on tumor necrosis factor-alpha expression and test the hypothesis that cold ischemia preceding warm ischemia causes overexpression of this cytokine. Rat livers were flushed out with University of Wisconsin solution and subjected to varying periods of warm ischemia, cold ischemia, or cold ischemia plus warm ischemia followed by reperfusion using a blood-free perfusion model. Tumor necrosis factor-alpha and interleukin-10 release into the perfusate and bile were measured by ELISA, and expression of these cytokines and that of c-fos, c-jun, and c-myc were studied by reverse-transcriptase polymerase chain reaction. We found high levels of tumor necrosis factor-alpha in the perfusates of livers subjected to warm ischemia-reperfusion, whereas minimal or no tumor necrosis factor-alpha was detected in livers subjected to cold ischemia-reperfusion or to cold ischemia plus warm ischemia-reperfusion. Reverse-transcriptase polymerase chain reaction confirmed the above findings and showed that immediate early genes were expressed in reperfused groups of livers. Measurements of cytokine release into bile showed that neither tumor necrosis factor-alpha nor interleukin-10 were upregulated by cold ischemia-reperfusion. The results suggest that (1) warm ischemia- and cold ischemia-reperfusion of rat liver lead to very different outcomes with regard to tumor necrosis factor-alpha expression and (2) cold ischemia preceding warm ischemia prevents upregulation of tumor necrosis factor-alpha.
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PMID:Marked difference in tumor necrosis factor-alpha expression in warm ischemia- and cold ischemia-reperfusion of the rat liver. 1122 27


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