leukotriene-b4 and Multiple-Organ-Failure

To investigate the changes in serum leukotrienes B4(LTB4) and p38 mitogen activated protein kinase (p38 MAPK) in multiple organ dysfunction syndrome (MODS) and to evaluate the relationship between LTB4 and p38 MAPK and clinical condition of patients with MODS.. The clinical condition of 26 patients with MODS was evaluated with scoring system. The serum LTB4 and p38 MAPK of the said patients and that of 12 healthy individuals were determined with enzyme linked immunoadsorbent assay(ELISA). The correlation of the scores of MODS and levels of serum LTB4 and p38 MAPK was analyzed. The correlation of the scores of MODS and levels of serum LTB4 and p38 MAPK was analyzed in non-survivors and survivors.. The serum level of LTB4[(923.96+/-308.65)ng/L] was significantly lower in MODS patients compared with control group [(2 453.31+/-400.93)ng/L, P<0.05]. There was no significant difference in serum level of p38 MAPK between the patients with MODS [(193.83+/-106.32)ng/L]ls and control group [(124.36+/- 84.50)ng/L, P>0.05]. There was significant difference in the serum level of LTB4 between the survivors[(1 334.51+/-530.35)ng/L] and non-survivors [(444.98+/-206.30)ng/L, P<0.05]. There were significant negative correlations between serum LTB4 and MODS scores (P<0.001).. The pathophysiological changes in later period of MODS are different from those of other common inflammatory responses. Serum LTB4 and p38 MAPK could be one of the indexes of the severity and prognosis on MODS.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Female; Humans; Leukotriene B4; Male; Middle Aged; Multiple Organ Failure; p38 Mitogen-Activated Protein Kinases; Young Adult

It has been suggested that multiple sublethal insults are commonly associated with the development of multiple organ failure (MOF). The gut is considered to be pivotal in the pathogenesis of MOF. This study investigated the effects of repeated ischemia-reperfusion of the rat small intestine.. Groups of rats underwent 30 min of superior mesenteric artery occlusion or sham operation followed by 24 h of reperfusion. They then received an additional 30 min of superior mesenteric artery occlusion and 2 h of reperfusion or sham operation. Small intestine was examined for mucosal injury, neutrophil infiltration, goblet cell number, and generation of the eicosanoids, prostaglandin E2, and leukotriene B4. Activation of neutrophils was assessed in systemic venous blood.. Animals subjected to two insults of ischemia-reperfusion demonstrated significantly less mucosal injury than animals undergoing one episode of ischemia and 2 h of reperfusion, despite increased neutrophil infiltration, leukotriene B4, and activated systemic neutrophils. Goblet cell number was elevated in animals 24 h after the first ischemia-reperfusion insult and remained enhanced after the second episode of ischemia-reperfusion.. The initial episode of ischemia-reperfusion caused an adaptive response associated with cytoarchitectural preservation following the subsequent insult. Increased mucus production was associated with mucosal protection. Nevertheless, repeated ischemia-reperfusion potentiated the local inflammatory response and the systemic activation of neutrophils.

Topics: Animals; Dinoprostone; Disease Models, Animal; Inflammation; Intestinal Mucosa; Intestine, Small; Leukotriene B4; Male; Multiple Organ Failure; Neutrophil Activation; Rats; Rats, Sprague-Dawley; Recurrence; Reperfusion Injury

In this study the authors assessed the sequential release of lipid mediators (TXB2, PGE2, 6-keto-PGF1alpha, LTB4, LTC4, PAF), pro-inflammatory cytokines (IL-6, IL-8, TNF-alpha) and anti-inflammatory cytokines (IL-4, IL-10) in 17 patients undergoing coronary artery bypass graft (CABG) with extracorporeal circulation (ECC). Time course of appearance of inflammatory mediators revealed the early and transient increase in lipid mediator plasma concentrations (6-keto-PGF1alpha, LTB4, LTC4, PAF) whereas cytokines (IL-6, IL-8, IL-10) were involved only in late pre- and post-operative periods. No variation of TXB2, PGE2, IL-4 and TNF-alpha levels were found. No correlation was documented between the levels of lipid mediators and pro- or anti-inflammatory cytokines suggesting that lipidic compounds are not implicated in the genesis of cytokines which appear much later involved. Despite the common use of high doses of aprotinin (a non-specific enzyme inhibitor) in hope to abrogate the inflammatory response to cardiopulmonary bypass procedure, this study reports the persistent release of several inflammatory compounds that might be involved in the post-CABG multiple organ failure syndromes.

Topics: 6-Ketoprostaglandin F1 alpha; Anti-Inflammatory Agents; Cardiopulmonary Bypass; Cytokines; Dinoprostone; Extracorporeal Circulation; Humans; Inflammation Mediators; Interleukin-10; Interleukin-4; Interleukin-6; Interleukin-8; Leukotriene B4; Leukotriene C4; Lipid Metabolism; Lipids; Multiple Organ Failure; Platelet Activating Factor; Prospective Studies; Thromboxane B2; Tumor Necrosis Factor-alpha

Ongoing clinical trials have revived interest in hypertonic saline (HTS) for postinjury resuscitation; these studies have documented serum Na+ concentrations > or = 170 mmol/L. Recent animal studies have shown that HTS enhances T-cell and monocyte function, but effects on the polymorphonuclear neutrophil (PMN) remain unclear. The postinjury lipid mediators platelet-activating factor (PAF) and leukotriene B4 (LTB4) have been implicated in PMN priming for cytotoxicity, which is believed to be important in the pathogenesis of multiple organ failure. We hypothesized that HTS would stimulate PMN superoxide (O2-) and elastase release from PAF- and LTB4-primed PMNs.. Isolated PMNs from five donors were primed for 5 minutes with 200 nmol/L PAF or 1 micromol/L LTB4 in Kreb's-Ringer's phosphate with dextrose at a Na+ concentration of 140 mmol/L (normal serum Na+ concentration), pelleted, and resuspended in Kreb's-Ringer's phosphate with dextrose for 10 minutes at a Na+ concentration of 130 to 170 mmol/L. O2- generation was measured by superoxide dismutase-inhibitable reduction of cytochrome c and elastase release by cleavage of N-methoxysuccinyl-Ala-Ala-Pro-Val p-nitroanilide.. HTS with Na+ concentration up to 170 mmol/L had no significant effect on O2- production or elastase release from quiescent cells. Na+ concentration of 160 and 170 mmol/L, however, activated PAF- and LTB4-primed PMNs for enhanced elastase release with no effect on O2- production.. In clinically relevant concentrations, elevated Na+ activates lipid-primed neutrophils for enhanced elastase degranulation. Consequently, the administration of HTS in the early postinjury resuscitation period, when PMNs are maximally primed, may activate PMN elastase release and thereby promote the development of multiple organ failure.

Topics: Humans; Leukotriene B4; Multiple Organ Failure; Multiple Trauma; Neutrophil Activation; Neutrophils; Osmolar Concentration; Pancreatic Elastase; Platelet Activating Factor; Resuscitation; Saline Solution, Hypertonic; Superoxides

The pathogenesis of multiple organ failure after injury is believed to involve priming and activation of the inflammatory cascade, and the polymorphonuclear neutrophil (PMN) appears to be an integral effector. Characterization of the primed PMN is evolving. Because much research has focused on the respiratory burst, the synergistic role of cytotoxic proteases, especially elastase, has been largely ignored. In addition, CD11b has been identified as pivotal in PMN-mediated tissue injury. Our hypothesis is that the well-recognized postinjury mediators platelet-activating factor (PAF) and leukotriene B4 (LTB4) prime PMNs for the concordant release of elastase and superoxide (O2-) as well as for CD11b up-regulation.. Human PMNs were isolated and then incubated with PAF or LTB4 before N-formyl-methionyl-leucyl-phenylalanine activation. O2- generation was measured by reduction of cytochrome c. Elastase was measured by cleavage of Ala-Ala-Pro-Val p-nitroanilide. CD11b expression was quantified by incubation with R-phycoerythrin-labeled monoclonal antibodies followed by flow cytometry.. PAF and LTB4 primed PMNs maximally within 5 minutes for the production of O2-, elastase release, and simultaneous up-regulation of CD11b expression on the PMN surface.. PAF and LTB4 prime human PMNs for the concordant release of elastase, generation of O2-, and CD11b up-regulation. Understanding the physiologic characteristics of PMN priming may offer new therapeutic targets to avoid the development of multiple organ failure after injury.

Topics: Humans; Inflammation; Leukocyte Elastase; Leukotriene B4; Macrophage-1 Antigen; Multiple Organ Failure; Neutrophils; Platelet Activating Factor; Respiratory Burst; Superoxides; Wounds and Injuries