interleukin-8 and Aortic-Dissection

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

In-hospital outcomes are generally acceptable in patients with type B dissection; however, some patients present with undesirable complications, such as aortic expansion and rupture. Excessive inflammation is an independent predictor of adverse clinical outcomes.. We have investigated the underlying mechanisms of catastrophic complications after acute aortic dissection (AAD) in mice.. When angiotensin II was administered in lysyl oxidase inhibitor-preconditioned mice, AAD emerged within 24 hours. The dissection was initiated at the proximal site of the descending thoracic aorta and propagated distally into an abdominal site. Dissection of the aorta caused dilatation, and ≈70% of the mice died of aortic rupture. AAD triggered CXCL1 and granulocyte-colony stimulating factor expression in the tunica adventitia of the dissected aorta, leading to elevation of circulating CXCL1/granulocyte-colony stimulating factor levels. Bone marrow CXCL12 was reduced. These chemokine changes facilitated neutrophil egress from bone marrow and infiltration into the aortic adventitia. Interference of CXCL1 function using an anti-CXCR2 antibody reduced neutrophil accumulation and limited aortic rupture post AAD. The tunica adventitia of the expanded dissected aorta demonstrated high levels of interleukin-6 (IL-6) expression. Neutrophils were the major sources of IL-6, and CXCR2 neutralization significantly reduced local and systemic levels of IL-6. Furthermore, disruption of IL-6 effectively suppressed dilatation and rupture of the dissected aorta without any influence on the incidence of AAD and neutrophil mobilization.. Adventitial CXCL1/granulocyte-colony stimulating factor expression in response to AAD triggers local neutrophil recruitment and activation. This leads to adventitial inflammation via IL-6 and results in aortic expansion and rupture.

Topics: Acute Disease; Adventitia; Aged; Aminopropionitrile; Angiotensin II; Animals; Antibodies, Monoclonal; Aorta, Thoracic; Aortic Aneurysm, Thoracic; Aortic Dissection; Aortic Rupture; Aortography; Chemokine CXCL1; Chemokine CXCL12; Chemotaxis, Leukocyte; Dilatation, Pathologic; Disease Models, Animal; Female; Granulocyte Colony-Stimulating Factor; Humans; Inflammation Mediators; Interleukin-6; Interleukin-8; Male; Mice, Inbred C57BL; Mice, Knockout; Middle Aged; Neutrophil Activation; Neutrophil Infiltration; Neutrophils; Receptors, Interleukin-8B; Signal Transduction; Time Factors

Enhanced stimulus-induced release of pro-inflammatory cytokines by leucocytes may contribute to the pathogenesis of ischaemic stroke.. We investigated the lipopolysaccharide-induced release of interleukin-1beta (IL-1beta), IL-6, IL-8, and tumour necrosis factor-alpha (TNF-alpha) in whole blood from 20 patients with a history of ischaemic stroke under the age of 50, 20 patients with a history of cervical artery dissection (CAD) and 21 age- and sex-matched healthy control subjects.. Release of IL-8 was higher (P = 0.006) and release of TNF-alpha and IL-6 tended to be higher (P < 0.1) in young stroke patients than in control subjects. No increased release existed in CAD patients. Vascular risk factors or history of infection before stroke did not modify IL-8 production. A common T(250) --> A polymorphism in the IL-8 gene promotor was newly identified but did not correlate with the variability of IL-8 release. The C(260) --> T polymorphism in the gene of the monocytic LPS-receptor CD14--a risk factor for myocardial infarction--was not associated with increased cytokine release.. We conclude that high inducible release of IL-8--and possibly of TNF-alpha and IL-6--may contribute to the odds of ischaemic stroke in young adults.

Topics: Adult; Aging; Aortic Dissection; Female; Humans; Interleukin-1; Interleukin-6; Interleukin-8; Leukocytes; Lipopolysaccharides; Male; Polymorphism, Genetic; Risk Factors; Stroke; 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