Gut ischemia and mesenteric synthesis of inflammatory cytokines after hemorrhagic or endotoxic shock

Abstract

The intestine plays a major role in the pathophysiology of multiorgan failure. Although the systemic inflammatory response might be induced by endotoxin released through bacterial translocation, other factors such as intestinal ischemia might be implicated. We investigated the relationship between intestinal ischemia-reperfusion and cytokine release in rat models of hemorrhagic or endotoxic shock. Plasma levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), lactate, and endotoxin, as well as macrophage TNF-alpha and IL-6 mRNA expression, were assessed at the end of shock and resuscitation. Hemodynamic changes and lactate levels suggested the presence of intestinal ischemia in both models. Mesenteric levels of TNF-alpha and IL-6 were increased by hemorrhage and further increased after saline resuscitation. Similar results were obtained with mRNA cytokine gene expression in macrophages. Endotoxin was not detectable in the hemorrhagic group. Endotoxic shock also increased production of cytokines, which, in contrast to hemorrhage, was not further increased by resuscitation. These results suggest that intestinal ischemia-reperfusion upon hemorrhage and resuscitation may be a major trigger for cytokine gene expression in the absence of endotoxin.

Intestinal Ischemia-Reperfusion Injury Alters Purinergic Receptor Expression in Clinically Relevant Extraintestinal Organs

“…Many associated pathophysiologic phenomena have been studied, some of which have been implicated as possible mediators of the extra-intestinal organ dysfunction seen during progression of SIRS to multiple organ failure (MOF) (5,6). Areas currently under investigation include the activation of local immune cells (7), alteration of intestinal permeability with subsequent bacterial translocation (8), changes in the local-regional production of inflammatory mediators (9), production of reactive oxygen species (10), changes in coagulation (11), and alteration in the expression of cellular adhesion molecules (12). Despite the extensive efforts in this field of study, the proximal cause of MOF secondary to IIR-induced SIRS has yet to be clearly elucidated.…”

Milk Fat Globule Epidermal Growth Factor 8 Attenuates Acute Lung Injury in Mice after Intestinal Ischemia and Reperfusion

“…Multiple organ failure, including acute lung injury (ALI), is a common complication of intestinal ischemia/reperfusion (I/R) injuries and contributes to its high mortality rate (2). ALI is caused by a systemic inflammatory response due to the release of proinflammatory cytokines and bacteria-derived endotoxins from reperfused ischemic tissue (3)(4)(5)(6). Only a limited number pharmacologic treatment options have been found that provide some benefit in I/R and ALI, most of them targeting inflammatory mediators and oxidative stress pathways (7).…”

A Trojan Horse in Intensive Care Unit: Toxoplasma gondii

“…20 During systemic inflammatory response syndrome and the compensatory anti-inflammatory response syndrome, the immune function may be impaired. [21][22][23][24] Individuals with immunity abnormalities such as ICU patients, who had been previously infected with T. gondii, may show increased IgG antibody titres or less frequently, increased titres of acute-phase antibodies, which may be interpreted as reactivation. T. gondii infection produces IgM, IgA, IgE and IgG antibodies, with the first three being detected early during the course of infection.…”