Pimenta MBP et al (original) (raw)
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IL-6 Release after Intestinal Ischemia/Reperfusion in Rats Is under Partial Control of TNF
Journal of Surgical Research, 1997
barrier may serve as potent inducers to stimulate the Although there is much evidence to substantiate the release of TNF, which would be critical in evoking the view that tumor necrosis factor (TNF) plays a pivotal deleterious effects of both local and systemic injury [9, role in the pathogenesis of multiple organ injury sub-10]. Moreover, prophylactic treatment with monoclonal sequent to intestinal ischemia/reperfusion (I/R), it is antibodies to TNFa protects against the development still unclear whether TNF is involved in triggering the of multiple organ or system dysfunction, including the release of other inflammatory mediators in this condilung, liver, intestines, and cardiovascular system, and tion. The current study was designed to determine the improves the survival rate following intestinal I/R inpotential effects of TNF blockade, by means of monosult [10-12].
The effect of transient intestinal ischemia on inflammatory parameters
International Journal of Colorectal Disease, 2003
Background and aims: To determine the early biological changes occurring in intestinal ischemia in vivo. Patients and methods: We studied the effects of acute transient intestinal ischemia in 15 patients undergoing elective open surgery for the treatment of abdominal subrenal aortic aneurysm induced by clamping of the aorta at subrenal level and above the branching of the inferior mesenteric artery. Blocking the blood flow results in hypoperfusion of the inferior mesenteric artery and then to rectal mucosal ischemia. Results: With the introduction of a mucosal ischemic period the basal intestinal mucosal pH decreased during ischemia, and showed a rapid increase during reperfusion to the level preceding ischemia. Parameters were evaluated in blood taken from inferior mesenteric vein. A rectal dialysis was put into the rectum to evaluate eicosanoid concentrations in rectal fluid collected before and during clamping and after declamping. Significant enhancement in plasma level of xanthine, a marker for tissue damage, was observed during reperfusion. Interleukin-6 levels were significantly elevated from 11.28±3.4 pg/ml (preischemic) to 109±85.9 pg/ml (ischemic) and to 189.33±120.24 pg/ml (reperfusion); and tromboxane B 2 levels from 141.57±51.20 pg/ml preoperation to 473.01±319.01 pg/ml during the surgical procedure. Conclusion: These observations indicate that even transient ischemia modifies the inflammatory pattern.
American Journal of Transplantation, 2004
Interleukin-6 (IL-6) is a pleiotropic acute reactant cytokine involved in inflammatory responses. To explore the role of IL-6 in inflammation, this study examined the efficacy of exogenous IL-6 in preventing intestinal ischemia/reperfusion (I/R) injury associated with small bowel transplantation (SBTx). Syngenic orthotopic SBTx was performed in Lewis rats after 6-h graft preservation in University of Wisconsin (UW) at 4 • C. IL-6 mutein (IL-6m, 500 lg/kg), a recombinant molecular variant of human IL-6, was subcutaneously given to donors 2 h before harvesting (IL-6mD) or to excised grafts by luminal infusion (IL-6mG). Animal survival was 100% and 75% in IL-6mD (p < 0.05 vs. control) and IL-6mG groups, respectively, compared with 64.3% in untreated controls. The severity of I/R injury (e.g. epithelial denudation, villous congestion) was reduced with IL-6m, in addition to a striking increase in re-epithelization. With IL-6m, neutrophil extravasation was markedly reduced in intestinal grafts and in remote organs (e.g. lung). IL-6m mediated antiinflammatory effects through the inhibition of I/Rinduced up-regulation of intragraft and circulating IL-1-b , tumor necrosis factor-a (TNF-a ) and IL-6. IL-6m also increased intestinal graft tissue blood flow. These results show that IL-6 is effective in protecting the intestine from cold I/R injury by maintaining graft blood flow and reducing pro-inflammatory cytokine up-regulation and neutrophil infiltration.
European Journal of Vascular and Endovascular Surgery, 2003
Objectives: a relationship has been demonstrated between increased intestinal permeability, endotoxaemia and the development of the systemic inflammatory response syndrome (SIRS) after aortic surgery. The aim of this study was to evaluate whether isolated lower limb ischaemia-reperfusion (I/R) injury affects intestinal mucosal barrier function and cytokine release. Patients and Methods: four groups of patients were investigated, group I, patients with critical limb ischaemia (CLI) undergoing infra-inguinal bypass surgery (n 18); group II, patients with intermittent claudication (IC) undergoing infra-inguinal bypass surgery (n 14); group III, patients with CLI unsuitable for arterial reconstruction, undergoing major amputation (n 12); and group IV, patients undergoing carotid endarterectomy for symptomatic carotid stenosis (n 13). Intestinal permeability, endotoxaemia and urinary soluble tumour necrosis factor receptors were assessed (p55TNF-R). Results: an increase in intestinal permeability was observed on the 3rd postoperative day only in CLI group. This was found to correlate with arterial clamp time. Patients who had a femoro-distal bypass had significantly higher intestinal permeability compared to those who had femoro-popliteal bypass. Endotoxaemia was not detected in any of the groups. Postoperative urinary p55TNF-R concentrations were significantly higher in CLI group compared to the other groups. These did not correlate with the increased intestinal permeability. Conclusions: our results support the hypothesis that revascularisation of critically ischaemia limbs leads to intestinal mucosal barrier dysfunction and cytokine release. They also suggest that the magnitude of the inflammatory response following I/R injury is related to the degree of initial ischaemia.
Interleukin-6 release in the hepatic blood outflow during normothermic liver ischaemia in humans
Digestive and Liver Disease, 2003
Background. Liver surgery techniques have consistently improved and normothermic ischaemia of the liver is considered to be a safe procedure to reduce intraoperative haemorrhage. Hepatic failure, however, remains a significant complication. In liver ischaemiareperfusion injury, cytokines play a key proinflammatory role. Cytokines may be part of the intercellular signalling that leads to recovery or to failure after major surgery. Moreover, they could be potential predictors of the outcome. Modulation of the pattern of cytokine response in the early postsurgery period could represent a new approach to minimise the impact of these procedures.
Journal of Surgical Research, 2001
Results. TNF-␣ and IL-1 levels in the intestinal tissue, and plasma TNF-␣ and endotoxin levels, were significantly (P < 0.05) reduced in the FR group. Severe mucosal damage on histological findings (120 min after reperfusion) and a large amount of intraluminal exudates (60 min after reperfusion) were shown in the NS group, but these findings were significantly (P < 0.05) ameliorated in the FR group. Serum AST levels in the NS group increased 120 min after reperfusion, but this change was significantly (P < 0.05) reduced in the FR group. The 30-day survival rate was 80% in the FR group and 30% in the NS group (P < 0.05).
High levels of portal TNF-α during abdominal aortic surgery in man
Cytokine, 1993
During shock or multiple organ dysfunction syndrome, translocation of bacteria and/or lipopolysaccharide (LPS) from the ischaemic gut might occur and could explain the excess of cytokine production detectable in plasma. To test this hypothesis, we studied a model of mild gut ischaemia due to bowel manipulation and aortic clamping in patients undergoing abdominal aortic surgery (n = 14). Per-operative levels of LPS and cytokines were measured before clamping and after reperfusion, and compared in systemic and portal blood. Systemic levels of LPS and cytokines were measured in a control group of patients undergoing internal carotid surgery (n = 7). Portal LPS was detectable (i.e., >12 pg/ml) in 36% of the patients undergoing aortic surgery after bowel manipulation, and in 71% after clamp release. Similar levels of LPS were observed in portal and systemic blood after clamp release. Circulating tumour necrosis factor alpha (TNF-o) was observed in all patients undergoing aortic surgery. Levels of portal TNF-o were higher than those in systemic blood after bowel manipulation as well as after reperfusion (P = 0.02 and 0.007, respectively). LPS was never detected in control patients and TNF-o was detectable in only two out of seven patients. Mean levels of IL-6 were similar in the two groups, with a peak on the day following surgery, confirming that circulating IL-6 is associated with any surgical procedures. Our data indicate that bowel manipulation, aortic clamping and reperfusion lead to similar levels of portal and systemic circulating LPS. High levels of portal TNF-cx as compared to systemic ones, suggest that the gut-associated macrophages, activated by bowel manipulation, mild ischaemia, and/or translocated LPS, are a probable source of TNF-o.
Ischaemia-Reperfusion Injury and Regional Inflammatory Responses in Abdominal Aortic Aneurysm Repair
European Journal of Vascular and Endovascular Surgery, 2004
Objectives. The inflammatory response to abdominal aortic aneurysm repair is likely to result in response to an ischaemiareperfusion injury (IRI) to the lower-limbs and gastrointestinal tract. This paper reviews the pathogenesis of the inflammatory response to abdominal aortic aneurysm repair, with specific reference to the levels of evidence in the current literature regarding the potential origin of the inflammatory response. Design. Review article. Methods. The current literature (1966( to August 2003 was reviewed specifically for all articles employing techniques of regional blood sampling from the venous drainage of the lower limbs or gastrointestinal tract during abdominal aortic aneurysm repair. Results. Ten relevant studies were identified. These demonstrated that regional blood sampling techniques could be easily performed, and provided useful information regarding the potential sites of origin of the inflammatory response. Conclusions. Regional blood sampling techniques provide useful information regarding the potential sites of origin of the inflammatory response. Current evidence suggests that both the lower limbs and gastrointestinal tract are clearly important in their roles, however more work is now required to compare directly the roles and contributions of the lower limbs and gastrointestinal tract to the inflammatory response during abdominal aortic aneurysm repair.