interleukin-8 and Aortic-Aneurysm

Type B acute aortic dissection (AAD) spares the ascending aorta and is optimally managed by medical therapy in the absence of complications. However, patients with enhanced inflammation sometimes present with aortic enlargement, thereby facing undesirable outcomes. Thus, a better understanding of the molecular and cellular mechanisms involved in AAD-associated inflammatory processes and the requirement for a novel therapeutic approach for patients with type B AAD are unmet clinical needs. This study showed that dissection per se induced neutrophil-chemoattractant chemokine expression in the aortic tunica adventitia, possibly by mechanical injury and stretching followed by pseudolumen formation. Subsequent systemic changes in chemokine-dependent signaling caused neutrophilia and massive neutrophil accumulation in the dissected aorta, thereby leading to aortic enlargement and rupture via interleukin-6 production. Importantly, temporal and spatial dynamics of inflammatory cytokine and chemokine elevation, as well as leukocyte recruitment, were consistent between rodents and humans. Our study provides a new mechanistic insight into neutrophil-mediated adventitial inflammation after AAD and implicates CXCR2- or interleukin-6 neutralization as novel therapeutic strategies to prevent large-artery complications, including aneurysm formation and rupture, in patients with type B AAD.

Topics: Acute Disease; Angiotensin II; Animals; Aorta; Aortic Aneurysm; Aortic Dissection; Chemokines; Gene Expression; Humans; Immune System Diseases; Interleukin-6; Interleukin-8; Leukocyte Disorders; Mice; Molecular Targeted Therapy; Neutrophils; Receptors, Interleukin-8B; Systemic Inflammatory Response Syndrome

To investigate effects of high-dose ulinastatin on the release of proinflammatory cytokines and lung injury in patients with aortic dissection after cardiopulmonary bypass (CPB) under deep hypothermic circulatory arrest (DHCA).. A prospective, randomized and double-blinded study.. A teaching hospital.. Thirty-six patients with acute type-A aortic dissection undergoing cardiac surgery using CPB under DHCA.. These patients randomly were selected to received total doses of 20,000 units/kg of ulinastatin (n = 18) or 0.9% saline (control, n = 18) at 3 time points (after anesthetic induction, before aortic cross-clamp, and after aortic cross-clamp release).. Tumor necrosis factor-alpha, interleukin 6, interleukin 8 and polymorphonuclear neutrophil elastase (PMNE) were measured after anesthetic induction (T0), 30 minutes (T1) after aortic cross-clamp, 3 (T2), 6 (T3) and 9 (T4) hours after weaning from CPB. Except for T1, pulmonary data, such as alveolar-arterial oxygen pressure difference, physiologic deadspace, peak inspiratory pressure, plateau pressure, static compliance and dynamic compliance, were obtained at the same time points. Concentrations of cytokines and PMNE were significantly lower in the ulinastatin group than the control group from T1 to T4, and peaked at T2 between the 2 groups. Compared with the pulmonary data of the control group at T2~T4, postoperative alveolar-arterial oxygen pressure difference, physiologic deadspace, peak inspiratory pressure, and plateau pressure significantly were lower, and static compliance and dynamic compliance higher in the ulinastatin group. Significantly shorter intubation time and intensive care unit stay were found in the ulinastatin group.. High-dose ulinastatin attenuates the elevation of cytokines and PMNE, reduces the pulmonary injury and improves the pulmonary function after CPB under DHCA. Consequently, it shortens the time of intubation and intensive care unit stay.

Topics: Anesthesia; Aorta; Aortic Aneurysm; Aortic Dissection; Cardiopulmonary Bypass; Circulatory Arrest, Deep Hypothermia Induced; Constriction; Cytokines; Female; Glycoproteins; Humans; Inflammation; Interleukin-6; Interleukin-8; Leukocyte Elastase; Male; Middle Aged; Monitoring, Intraoperative; Postoperative Care; Respiratory Function Tests; Sternotomy; Trypsin Inhibitors; Tumor Necrosis Factor-alpha

The objective of this study is to evaluate the inflammatory response caused by endovascular stents in the treatment of aortic aneurysms.. Twenty-five patients underwent endovascular stent treatment from March through December 2005. The evolution of mediators (sedimentation velocity, C reactive protein, interleukin-6, interleukin-8, tumor necrosis factor-alpha, intercellular adhesion molecule-1, l-selectin), inflammatory cells (leukocytes, lymphocytes, platelets), serum creatinine and body temperature within preoperative period and in the following postoperative periods--1, 6, 24 and 48 h, 7 days, 1-3 months, was analyzed. In order to achieve statistic significance, Friedman test and Wilcoxon test were used, with index of significance of 5% (p<0.05).. Peak values of sedimentation velocity, C reactive protein and interleukin-6 were observed at 7 days (p<0.0001), 48 h (p<0.0001) and 24h (p<0.0001), respectively. Tumor necrosis factor-alpha and interleukin-8 did not show statistically significant variability during the entire follow-up. In terms of intercellular adhesion molecule-1 and l-selectin, their expressive values were found in late phase of follow-up, although without statistical significance. Elevation of leukocytes count occurred in premature phase of follow-up (p<0.0001), while lymphocyte and platelet count occurred in a late phase of follow-up (p<0.0001). Serum levels of creatinine did not show significant variability during follow-up. The period between 24 and 48 h corresponded to major frequency for fever (p<0.0001).. Individual mediators analysis and inflammatory cells demonstrated variability of their values during postoperative follow-up. This could help in the analysis of the inflammatory response evolution caused by endovascular stent treatment for aortic aneurysms in premature and late phases after implantation of the vascular prosthesis.

Topics: Adult; Aged; Aged, 80 and over; Aortic Aneurysm; Aortic Aneurysm, Abdominal; Aortic Aneurysm, Thoracic; Blood Vessel Prosthesis Implantation; Female; Follow-Up Studies; Humans; Inflammation; Inflammation Mediators; Intercellular Adhesion Molecule-1; Interleukin-6; Interleukin-8; L-Selectin; Male; Middle Aged; Stents; Tumor Necrosis Factor-alpha

In the early phase after the onset of acute aortic dissection, oxygenation impairment often occurs. However, the etiology and clinical course of this phenomenon have not been established. We examined the serial changes of oxygenation, inflammatory reaction and laboratory data in patients with acute aortic dissection.. Nine patients (DeBakey type I; 4, type II; 3 and type IIIb; 2), aged 46 to 82 years were included in this study. All patients were managed in the intensive care unit, and systolic arterial pressure was maintained at around 110 to 120 mm Hg. Oxygenation was impaired in all patients, three (33%) of whom required mechanical ventilatory support.. Pleural effusion was observed in eight (89%) of nine patients. Respiratory index was 0.98+/-0.19 (mean +/-SEM) at the time of admission, and elevated to 1.59+/-0.35, 1.58+/-0.21, 1.60+/-0.28 respectively, at day 1, 2 and 3. Oxygenation index was 318+/-34 at the time of admission, and decreased to 271+/-34, 255+/-19, 263+/-26, respectively, at day 1, 2 and 3. These values recovered to normal after day 4. The increase of white blood cells and high fever (>38 degrees C) continued until day 3. Platelet counts recovered after day 4. The serum bilirubin level was highest (2.0+/-0.5 mg/dl) at day 3, and decreased gradually after day 4. In two recent patients whose serum interleukin-8 (IL-8) was measured, IL-8 levels increased according to the impaired oxygenation or aneurysmal enlargement. Impaired oxygenation, inflammatory changes, platelet consumption and bilirubin elevation continued until day 3 and resumed normal levels after day 4.. These changes may be due to hemolysis, consumption coagulopathy or inflammation associated with acute aortic dissection. IL-8 elevation may be associated with aneurysmal enlargement and these phenomena.

Topics: Aged; Aged, 80 and over; Aortic Aneurysm; Aortic Dissection; Bilirubin; Female; Humans; Interleukin-8; Lung; Male; Middle Aged; Oxygen; Respiration