34 results on '"Capillary Leak Syndrome immunology"'
Search Results
2. Nivolumab-induced systemic capillary leak syndrome as an ultra rare life-threatening phenomenon of late toxicity and intravenous immunoglobulin efficacy.
- Author
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Polishchuk I, Yakobson A, Zemel M, A Sharb A, Shalata W, Rosenberg E, A Kian T, Alguayn F, Peled N, Rouvinov K, Alguayn W, and Kian W
- Subjects
- Adrenal Cortex Hormones therapeutic use, Capillary Leak Syndrome therapy, Fluid Therapy methods, Humans, Male, Middle Aged, Treatment Outcome, Capillary Leak Syndrome chemically induced, Capillary Leak Syndrome immunology, Immune Checkpoint Inhibitors adverse effects, Immunoglobulins, Intravenous therapeutic use, Nivolumab adverse effects
- Abstract
Systemic capillary leak syndrome (SCLS) is a life-threatening disease. It is characterized by severe capillary hyperpermeability to proteins resulting in hemoconcentration, hypoalbuminemia and hypovolemic shock. Its treatment remains supportive, and the prognosis is generally poor. We report on a 51-year old male with melanoma treated with nivolumab for 1 year. 1 month following the completion of the treatment, the patient presented with signs of hypovolemic shock, anasarca, hemoconcentration and hypoalbuminemia. After excluding other diseases, a diagnosis of nivolumab-induced systemic capillary leak syndrome was made. A high dose of intravenous steroid therapy was promptly initiated without any significant clinical improvement. Intravenous immunoglobulin therapy was then administered with normalization of blood pressure, hemoconcentration and complete resolution of anasarca. Intravenous immunoglobulin should be considered a first-line treatment option for this rare phenomenon.
- Published
- 2021
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3. C1 esterase inhibitor in pediatric cardiac surgery with cardiopulmonary bypass plays a vital role in activation of the complement system.
- Author
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Miyamoto T, Ozaki S, Inui A, Tanaka Y, Yamada Y, and Matsumoto N
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- Administration, Intravenous, Capillary Leak Syndrome blood, Capillary Leak Syndrome diagnosis, Capillary Leak Syndrome immunology, Complement C1 Inhibitor Protein adverse effects, Complement Inactivating Agents adverse effects, Female, Heart Defects, Congenital blood, Heart Defects, Congenital diagnostic imaging, Heart Defects, Congenital immunology, Humans, Infant, Infant, Newborn, Japan, Male, Prospective Studies, Systemic Inflammatory Response Syndrome blood, Systemic Inflammatory Response Syndrome diagnosis, Systemic Inflammatory Response Syndrome immunology, Time Factors, Treatment Outcome, Capillary Leak Syndrome prevention & control, Cardiac Surgical Procedures adverse effects, Cardiopulmonary Bypass adverse effects, Complement Activation drug effects, Complement C1 Inhibitor Protein administration & dosage, Complement Inactivating Agents administration & dosage, Heart Defects, Congenital surgery, Systemic Inflammatory Response Syndrome prevention & control
- Abstract
Our prospective study was therefore designed to determine which part of the systemic inflammatory response after cardiac operations resulted from Cardiopulmonary bypass (CPB) in neonates and infants. After approval by the human ethical committee of the Gunma Children's Medical Center (GCMC) and informed consent of the parents, 40 consecutive term congenital heart disease patients aged until 1 year who underwent long CPB time (> 3 h) at surgery were included in the prospective study between January 2012 and December 2014. C1 esterase inhibitor (C1-inh) drug (@Berinert) was generously provided by CSL Behring (King of Prussia, PA). The C1-inh (20 IU/kg) was given intravenously 60 min after CPB. Blood samples for complement factors were obtained before and 48 h after administration of C1-inh. Six patients did not survive and their data were not included. Of 34 patients included, median age was 6.5 months, median body weight was 6050 g, and 16 (47%) were female. According to the Mann-Whitney U test, there were no differences between the two groups concerning demographic and intraoperative data, postoperative chemical data. C1q concentration was only significant lower in patients with C1-inh non-treated group than in patients with C1-inh treated group. But, the consumption of C1q, C3, C4, CH
50 , and C1-inh in patients with C1-inhibitor non-treated group was observed early postoperatively. There is a significant difference in the values before and after C1-inh treatment between the two groups. The lower value in the C1-inh-treated group is explained by the activation of the classical pathway through the replenishment of complements by C1-inh treatment. This study proposes the administration of C1-inh is an effective therapy to reduce the activation and improve the clinical capillary leak syndrome.- Published
- 2020
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4. Systemic Capillary Leak Syndrome (Clarkson's Disease) as a Complication of Anti-Programmed Death 1 Immunotherapy.
- Author
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Lescure C, Lescoat A, Salé A, Bazin Y, Duvergé L, Desrues B, and Léna H
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- Antineoplastic Combined Chemotherapy Protocols therapeutic use, Capillary Leak Syndrome immunology, Cisplatin administration & dosage, Female, Humans, Lung Neoplasms immunology, Middle Aged, Nivolumab administration & dosage, Nivolumab adverse effects, Pemetrexed administration & dosage, Antineoplastic Combined Chemotherapy Protocols adverse effects, Capillary Leak Syndrome chemically induced, Immunotherapy methods, Lung Neoplasms drug therapy, Programmed Cell Death 1 Receptor antagonists & inhibitors
- Published
- 2019
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5. Clinical communication: systemic capillary leak syndrome due to mast cell activation?
- Author
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Van Winkle RC, Malatack JJ, Schwartz LB, and McGeady SJ
- Subjects
- Anaphylaxis blood, Anaphylaxis immunology, Capillary Leak Syndrome blood, Capillary Leak Syndrome immunology, Child, Diagnosis, Differential, Humans, Male, Tryptases blood, Anaphylaxis diagnosis, Capillary Leak Syndrome diagnosis, Mast Cells immunology
- Published
- 2019
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6. Characterizing drug-induced capillary leak syndromes using the World Health Organization VigiBase.
- Author
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Mertz P, Lebrun-Vignes B, Salem JE, and Arnaud L
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- Antineoplastic Agents administration & dosage, Capillary Leak Syndrome immunology, Humans, Immunologic Factors administration & dosage, Male, Retrospective Studies, World Health Organization, Antineoplastic Agents adverse effects, Capillary Leak Syndrome chemically induced, Capillary Leak Syndrome epidemiology, Databases, Factual, Immunologic Factors adverse effects
- Published
- 2019
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7. Probable Mechanisms Involved in Immunotoxin Mediated Capillary Leak Syndrome (CLS) and Recently Developed Countering Strategies.
- Author
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Darvishi B, Farahmand L, Jalili N, and Majidzadeh-A K
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- Animals, Humans, Inflammation chemically induced, Inflammation immunology, Inflammation pathology, Inflammation therapy, Capillary Leak Syndrome chemically induced, Capillary Leak Syndrome immunology, Capillary Leak Syndrome pathology, Capillary Leak Syndrome therapy, Cytokines immunology, Immunotoxins adverse effects, Immunotoxins therapeutic use, Killer Cells, Lymphokine-Activated immunology, Killer Cells, Lymphokine-Activated pathology, Neoplasms drug therapy, Neoplasms immunology, Neoplasms pathology
- Abstract
Antibody-toxin fused agents or immunotoxins, are a newly engineered class of cytotoxic agents consisting of a bacterial or plant toxin moiety hooked up either to a monoclonal antibody or a specific growth factor. Nevertheless, acquiring a full potency in clinic is mostly restricted due to the Capillary leak syndrome (CLS), a serious immune provoked, life-threatening side effect, subsequent to the endothelial damage, resulting in fluid escape from the bloodstream into tissues including lungs, muscle and brain, developing organ failure and eventually death. Proposed underlying mechanisms include direct damage to endothelial cells, acute inflammation, Lymphokine-activated killer (LAK) cells engagement, alteration in cell-cell/cell-matrix connectivities and cytoskeletal dysfunction. Very poor biodistribution and heterogeneous extravasation pattern in tumor site result in accumulation of ITs close to the extravasation site, gradual toxin release and initiation of nearby endothelial cells lysis, secretion of pro-inflammatory cytokines, development of acute inflammation and engagement of Lymphokine-activated killer (LAK) cells. Intrinsic immunogenicity of applied toxin moiety is another important determinant of CLS incidence. Toxins with more intrinsic immunogenicity possess more probability for CLS development. Recently, development of new generations of antibodies and mutated toxins with conserved cytotoxicity has partly tapered risk of CLS development. Here, we describe probable mechanisms involved in CLS and introduce some of the recently applied strategies for lessening incidence of CLS as much as possible., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)
- Published
- 2018
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8. Engraftment Syndrome after Autologous Stem Cell Transplantation: An Update Unifying the Definition and Management Approach.
- Author
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Cornell RF, Hari P, and Drobyski WR
- Subjects
- Brain Diseases etiology, Brain Diseases immunology, Brain Diseases pathology, Brain Diseases therapy, Capillary Leak Syndrome etiology, Capillary Leak Syndrome immunology, Capillary Leak Syndrome pathology, Capillary Leak Syndrome therapy, Diarrhea etiology, Diarrhea immunology, Diarrhea pathology, Diarrhea therapy, Exanthema etiology, Exanthema immunology, Exanthema pathology, Exanthema therapy, Fever etiology, Fever immunology, Fever pathology, Fever therapy, Graft vs Host Disease immunology, Graft vs Host Disease pathology, Hematopoietic Stem Cell Transplantation adverse effects, Hepatic Insufficiency etiology, Hepatic Insufficiency immunology, Hepatic Insufficiency pathology, Hepatic Insufficiency therapy, Humans, Lymphoma immunology, Lymphoma pathology, Multiple Myeloma immunology, Multiple Myeloma pathology, POEMS Syndrome immunology, POEMS Syndrome pathology, Renal Insufficiency etiology, Renal Insufficiency immunology, Renal Insufficiency pathology, Renal Insufficiency therapy, Risk Factors, Transplantation Conditioning, Transplantation, Autologous, Graft vs Host Disease therapy, Hematopoietic Stem Cell Transplantation methods, Immunosuppressive Agents therapeutic use, Lymphoma therapy, Multiple Myeloma therapy, POEMS Syndrome therapy
- Abstract
Engraftment syndrome (ES) encompasses a continuum of periengraftment complications after autologous hematopoietic stem cell transplantation. ES may include noninfectious fever, skin rash, diarrhea, hepatic dysfunction, renal dysfunction, transient encephalopathy, and capillary leak features, such as noncardiogenic pulmonary infiltrates, hypoxia, and weight gain with no alternative etiologic basis other than engraftment. Given its pleiotropic clinical presentation, the transplant field has struggled to clearly define ES and related syndromes. Here, we present a comprehensive review of ES in all documented disease settings. Furthermore, we discuss the proposed risk factors, etiology, and clinical relevance of ES. Finally, our current approach to ES is included along with a proposed treatment algorithm for the management of this complication., (Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)
- Published
- 2015
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9. Invasive pulmonary aspergillosis in a patient presenting with idiopathic systemic capillary leak syndrome.
- Author
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Hayama M, Shime N, and Mio T
- Subjects
- Capillary Leak Syndrome complications, Capillary Leak Syndrome immunology, Humans, Invasive Pulmonary Aspergillosis complications, Invasive Pulmonary Aspergillosis immunology, Male, Middle Aged, Opportunistic Infections complications, Opportunistic Infections immunology, Radiography, Antifungal Agents therapeutic use, Capillary Leak Syndrome therapy, Invasive Pulmonary Aspergillosis drug therapy, Lung diagnostic imaging, Opportunistic Infections drug therapy
- Abstract
A 54-year-old man presented to our emergency department with fever and dyspnoea. He required vigorous haemodynamic support and mechanical ventilation for hypotensive distributive shock with hypoalbuminaemia, haemoconcentration, rhabdomyolysis and acute renal failure, consistent with idiopathic systemic capillary leak syndrome. Left lung consolidation and hypoxaemia were observed 6 days after admission. Sputum smear revealed the presence of acute angled branching hyphae, consistent with a diagnosis of invasive pulmonary aspergillosis. Antifungal therapy was administered and mechanical ventilation discontinued on day 66. The patient recovered and was discharged from the hospital on day 185., (2014 BMJ Publishing Group Ltd.)
- Published
- 2014
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10. Intravenous immunoglobulin in systemic capillary leak syndrome: a case report and review of literature.
- Author
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Marra AM, Gigante A, and Rosato E
- Subjects
- Capillary Leak Syndrome immunology, Capillary Permeability drug effects, Clinical Trials as Topic, Disease-Free Survival, Edema etiology, Europe, Humans, Male, Middle Aged, Recurrence, Shock etiology, Terbutaline administration & dosage, Theophylline administration & dosage, Capillary Leak Syndrome therapy, Edema prevention & control, Immunoglobulins, Intravenous therapeutic use, Shock prevention & control
- Abstract
The systemic capillary leak syndrome (SCLS) is a rare condition characterized by unexplained episodic attacks of systemic capillary hyperpermeability accompanied by hypoalbuminemia, hemoconcentration and edema. Treatment of the acute phase is supportive, focusing on adequate fluid resuscitation. Many agents have been used to prevent acute attacks, including corticosteroids, β2-agonists (aminophylline, theophylline, or terbutaline), infliximab, thalidomide and intravenous immunoglobulin (IVIg). β2-agonists were the first-line maintenance therapy until a few years ago. In more recent years, IVIg became common first-line prophylactic therapy in most patients with benefits at the dose of 2 g/kg once a month. We report the case of a 49-year-old man with SCLS treated successfully with a lower dose of IVIg (1 g/kg monthly) in the maintenance phase. He presented no acute episodes in a follow-up of 28 months. We describe prophylactic treatments for SCLS in literature and compare our patient to another 18 who received IVIg in follow-up.
- Published
- 2014
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11. [Microvascular effects of burn plasma transfer and therapeutic options in a rat model].
- Author
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Hernekamp JF, Harenberg PS, Lehnhardt M, Germann G, Walther A, and Kremer T
- Subjects
- Animals, Anti-Infective Agents, Local pharmacology, Antioxidants pharmacology, Ascorbic Acid pharmacology, Blood Flow Velocity drug effects, Blood Flow Velocity physiology, Burns drug therapy, Capillary Leak Syndrome drug therapy, Cell Adhesion drug effects, Cerium pharmacology, Extravasation of Diagnostic and Therapeutic Materials, Leukocytes drug effects, Male, Mesenteric Veins drug effects, Mesenteric Veins immunology, Microcirculation drug effects, Rats, Rats, Wistar, Shock drug therapy, Venules drug effects, Venules immunology, Burns immunology, Capillary Leak Syndrome immunology, Cell Adhesion immunology, Cytokines physiology, Disease Models, Animal, Edema immunology, Leukocytes immunology, Microcirculation immunology, Plasma immunology, Shock immunology
- Abstract
Introduction: Thermal injuries with more than 20% of burned body surface area (BSA) lead to systemic shock with generalised oedema in addition to local tissue destruction. This condition, known as burn injury, is caused by immunmodulative mediators whose individual significance is not known in detail. We present an experimental model where plasma of burned animals (burn plasma) is transmitted to healthy animals, to trigger burn iniury without performing direct burn trauma., Material and Methods: The systemic oedema is measured by extravasation of fluorescent albumin in mesenterial venules of Wistar rats. In addition, leukocyte-endothelial interactions ("leukocyte rolling and sticking") is examined., Results: The systemic capillary leak is induced by both direct thermal trauma as well as by infusion of burn plasma. This is evident even after plasma dilution (1% in Ringer's lactate) of the burn plasma. In addition, topical therapy for burned animals (donors) with cerium nitrate led to a significant reduction of plasma extravasation in receiver animals. In addition, systemic antioxidant therapy with high-dose vitamin C of receiver animals, led to a significant reduction of the capillary leak. Leukocyte-endothelial interactions are not significantly affected in either case., Conclusion: In summary, for the first time a reliable model of burn injury has been established, which eliminates mediator-independent effects. In addition, our studies show that antioxidant therapy with high doses of vitamin C and topical treatment with cerium nitrate both reduce the systemic capillary leak in receiver animals. Their positive influence could therefore soon be integrated in clinical treatment algorithms., (© Georg Thieme Verlag KG Stuttgart · New York.)
- Published
- 2012
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12. Idiopathic systemic capillary leak syndrome: novel therapy for acute attacks.
- Author
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Dowden AM, Rullo OJ, Aziz N, Fasano MB, Chatila T, and Ballas ZK
- Subjects
- Acute Disease, Aminophylline therapeutic use, Anti-Inflammatory Agents therapeutic use, Antibodies, Monoclonal therapeutic use, Capillary Leak Syndrome immunology, Capillary Permeability drug effects, Child, Cytokines blood, Female, Humans, Immunologic Factors therapeutic use, Infliximab, Male, Middle Aged, Tumor Necrosis Factor-alpha immunology, Capillary Leak Syndrome drug therapy, Phosphodiesterase Inhibitors therapeutic use, Terbutaline therapeutic use, Theophylline therapeutic use, Tumor Necrosis Factor-alpha antagonists & inhibitors
- Published
- 2009
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13. Blockade of hyaluronan inhibits IL-2-induced vascular leak syndrome and maintains effectiveness of IL-2 treatment for metastatic melanoma.
- Author
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Guan H, Nagarkatti PS, and Nagarkatti M
- Subjects
- Animals, Apoptosis immunology, Capillary Leak Syndrome pathology, Carrier Proteins metabolism, Cell Differentiation immunology, Cytotoxicity, Immunologic, Endothelium, Vascular cytology, Endothelium, Vascular immunology, Endothelium, Vascular pathology, Female, Hyaluronan Receptors metabolism, Hyaluronic Acid biosynthesis, Hyaluronic Acid metabolism, Interleukin-2 physiology, Killer Cells, Lymphokine-Activated cytology, Killer Cells, Lymphokine-Activated immunology, Lung Neoplasms blood supply, Lung Neoplasms pathology, Lung Neoplasms secondary, Lymphocytes, Tumor-Infiltrating immunology, Lymphocytes, Tumor-Infiltrating pathology, Melanoma, Experimental blood supply, Melanoma, Experimental pathology, Mice, Mice, Inbred C57BL, Mitochondrial Proteins, Capillary Leak Syndrome immunology, Capillary Leak Syndrome prevention & control, Hyaluronic Acid antagonists & inhibitors, Interleukin-2 administration & dosage, Interleukin-2 antagonists & inhibitors, Lung Neoplasms prevention & control, Melanoma, Experimental immunology, Melanoma, Experimental therapy
- Abstract
Vascular leak syndrome (VLS) is a life-threatening toxicity induced during IL-2 treatment of cancer patients. The mechanism of IL-2-induced VLS is still poorly understood. At present, there is no specific therapy for VLS. Previous studies from our laboratory demonstrated that hyaluronan (HA), a large glycosaminoglycan, abundant in the extracellular matrix and on the cell surface, caused a marked increase of IL-2-induced VLS in the lungs and liver of C57BL/6 mice. Conversely, blockade or knockout of its major receptor, CD44, resulted in a marked decrease of VLS, thereby suggesting a role for HA in VLS. In this study, we report a novel means to prevent IL-2-induced VLS by blocking endogenous HA with HA-specific binding peptide, Pep-1, a newly isolated peptide which specifically binds to soluble, cell-associated, and immobilized forms of HA. Our results demonstrated that blocking HA with Pep-1 dramatically inhibited IL-2-induced VLS in both normal mice as well as in mice bearing melanoma. Moreover, Pep-1 treatment maintained the effectiveness of IL-2 and prevented the metastasis of melanoma. IL-2-induced emigration of lymphocytes across the endothelium and cytotoxicity against tumor by lymphokine-activated killer cells were not affected by Pep-1. Instead, use of Pep-1 maintained endothelial integrity and reduced their apoptosis during IL-2-induced VLS. These data suggested that HA plays a critical role in regulating endothelial cell damage and induction of IL-2-mediated VLS. Also, blockade of HA using Pep-1 could constitute a novel therapeutic modality to prevent IL-2-mediated toxicity, thereby facilitating the effectiveness of high-dose IL-2 in the treatment of metastatic melanomas.
- Published
- 2007
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14. Suppression of endotoxin-induced inflammation by taxol.
- Author
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Mirzapoiazova T, Kolosova IA, Moreno L, Sammani S, Garcia JG, and Verin AD
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- Animals, Bronchoalveolar Lavage Fluid immunology, Capillary Leak Syndrome immunology, Capillary Leak Syndrome pathology, Endotoxemia pathology, Extravasation of Diagnostic and Therapeutic Materials immunology, Extravasation of Diagnostic and Therapeutic Materials pathology, Leukocyte Count, Lung immunology, Lung pathology, Mice, Mice, Inbred C57BL, Peritonitis immunology, Peritonitis pathology, Peroxidase metabolism, Pulmonary Edema immunology, Pulmonary Edema pathology, Respiratory Distress Syndrome pathology, Systemic Inflammatory Response Syndrome pathology, Endotoxemia immunology, Lipopolysaccharides immunology, Paclitaxel pharmacology, Respiratory Distress Syndrome immunology, Systemic Inflammatory Response Syndrome immunology, Tubulin Modulators pharmacology
- Abstract
The pathogenesis of acute lung injury includes transendothelial diapedesis of leukocytes into lung tissues and disruption of endothelial/epithelial barriers leading to protein-rich oedema. In vitro studies show that the microtubule network plays a role in the regulation of endothelial permeability as well as in neutrophil locomotion. It was hypothesised that the microtubule-stabilising agent, taxol, might attenuate inflammation and vascular leak associated with acute lung injury in vivo. The effect of intravenously delivered taxol was assessed using a model of murine lung injury induced by intratracheal lipopolysaccharide (LPS) administration. Parameters of lung injury and inflammation were assessed 18 h after treatment. Intravenously delivered taxol significantly reduced inflammatory histological changes in lung parenchyma and parameters of LPS-induced inflammation: infiltration of proteins and inflammatory cells into bronchoalveolar lavage fluid, lung myeloperoxidase activity, and extravasation of Evans blue-labelled albumin into lung tissue. Taxol alone (in the absence of LPS) had no appreciable effect on these parameters. In addition to lung proteins, intravenous taxol reduced accumulation of leukocytes in ascitic fluid in a model of LPS-induced peritonitis. Taken together, the present data demonstrate that microtubule stabilisation with taxol systemically attenuates lipopolysaccharide-induced inflammation and vascular leak.
- Published
- 2007
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15. Vascular biology in sepsis: pathophysiological and therapeutic significance of vascular dysfunction.
- Author
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Matsuda N and Hattori Y
- Subjects
- Animals, Apoptosis, Blood Coagulation Factors metabolism, Capillary Leak Syndrome immunology, Capillary Leak Syndrome metabolism, Dilatation, Pathologic blood, Dilatation, Pathologic immunology, Dilatation, Pathologic physiopathology, Endothelial Cells metabolism, Endothelial Cells pathology, Endothelium, Vascular immunology, Humans, Microcirculation immunology, Shock, Septic immunology, Endothelium, Vascular physiopathology, Microcirculation physiopathology, Shock, Septic blood, Shock, Septic physiopathology
- Abstract
Sepsis is the leading cause of mortality in critically ill patients. In this pathological syndrome, septic shock and sequential multiple organ failure correlate with poor outcome. The pathophysiology of sepsis with acute organ dysfunction involves a highly complex, integrated response that includes activation of number of cell types, inflammatory mediators, and the hemostatic system. Central to this process may be alterations in vascular functions. This review article provides a growing body of evidence for the potential impact of vascular dysfunction on sepsis pathophysiology with a major emphasis on the endothelium. Furthermore, the role of apoptotic signaling molecules in the mechanisms underlying endothelial cell injury and death during sepsis and its potential value as a target for sepsis therapy will be discussed, which may help in the assessment of ongoing therapeutic strategies.
- Published
- 2007
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16. [Clarkson syndrome: a rare clinical condition characterized by generalized edema associated to monoclonal gammopathy].
- Author
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Vella FS, Panella E, Masciale N, Giannelli G, and Antonaci S
- Subjects
- Adrenergic beta-Agonists therapeutic use, Albuterol therapeutic use, Aminophylline therapeutic use, Angioedema immunology, Angioedema physiopathology, Angioedema therapy, Anti-Inflammatory Agents therapeutic use, Blood Transfusion, Capillary Leak Syndrome immunology, Capillary Leak Syndrome physiopathology, Capillary Leak Syndrome therapy, Capillary Permeability, Cardiotonic Agents therapeutic use, Drug Therapy, Combination, Humans, Interleukin-2 metabolism, Male, Middle Aged, Monoclonal Gammopathy of Undetermined Significance immunology, Monoclonal Gammopathy of Undetermined Significance physiopathology, Monoclonal Gammopathy of Undetermined Significance therapy, Prednisone therapeutic use, Treatment Outcome, Angioedema diagnosis, Capillary Leak Syndrome diagnosis, Monoclonal Gammopathy of Undetermined Significance diagnosis
- Abstract
Generalized edema is commonly due to cardiac failure, renal changes, hepatic and metabolic disturbances, or it can be idiopathic, i.e. primitive lymphedema. Here we describe a patient with several episodes of fluid extravasation characterized by hypotension, hemoconcentration and functional renal insufficiency. These findings, associated to a monoclonal gammopathy, lead to the diagnosis of systemic capillary leak syndrome or Clarkson Syndrome. This rare and perplexing disorder, characterized by a typical three-phase clinical feature, is due to an endothelium permeability alteration, rather responsible of these paroxysmal manifestations. Interleukin-2-pathway is considered as one of the underlying mechanisms. During acute phase the patient underwent therapy with plasma-expanders and glucocorticoids, although in quiescent phase we administered aminophylline, salbutamol and prednisone. After three months, the patient is asymptomatic.
- Published
- 2005
17. Inhibition of the Src and Jak kinases protects against lipopolysaccharide-induced acute lung injury.
- Author
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Severgnini M, Takahashi S, Tu P, Perides G, Homer RJ, Jhung JW, Bhavsar D, Cochran BH, and Simon AR
- Subjects
- Adenoviridae genetics, Animals, Capillary Leak Syndrome genetics, Capillary Leak Syndrome immunology, Enzyme Activation drug effects, Enzyme Activation genetics, Enzyme Activation immunology, Escherichia coli, Gene Expression Regulation drug effects, Gene Transfer Techniques, Indoles pharmacology, Janus Kinase 2, Lung drug effects, Lung immunology, Lung pathology, Mice, Mice, Inbred BALB C, Protein-Tyrosine Kinases genetics, Proto-Oncogene Proteins genetics, Respiratory Distress Syndrome pathology, Signal Transduction drug effects, Signal Transduction genetics, Sulfonamides pharmacology, Transcriptional Activation immunology, Tyrphostins pharmacology, src-Family Kinases genetics, Enzyme Inhibitors pharmacology, Lipopolysaccharides immunology, Protein-Tyrosine Kinases antagonists & inhibitors, Proto-Oncogene Proteins antagonists & inhibitors, Respiratory Distress Syndrome immunology, src-Family Kinases antagonists & inhibitors
- Abstract
The cascade of cellular and molecular pathways mediating acute lung injury is complex and incompletely defined. Although the Src and Jak family of kinases is upregulated in LPS-induced murine lung injury, their role in the development of lung injury is unknown. Here we report that systemic inhibition of these kinases using specific small molecule inhibitors (PP2, SU6656, tyrphostin A1) significantly attenuated LPS-induced lung injury, as determined by histologic and capillary permeability assays. These inhibitors blocked LPS-dependent cytokine and chemokine production in the lung and in the serum. In contrast, lung-targeted inhibition of these kinases in the airway epithelium via adenoviral-mediated gene transfer of dominant negative Src or of suppressor of cytokine signaling (SOCS-1) disrupted lung cytokine production but had no effect on systemic cytokine production or lung vascular permeability. Mice were significantly protected from lethal LPS challenge by the small molecule inhibitors of Jak and Src kinase. Importantly, this protection was still evident even when the inhibitors were administered 6 hours after LPS challenge. Taken together, these observations suggest that Jak and Src kinases participate in acute lung injury and verify the potential of this class of selective tyrosine kinase inhibitors to serve as novel therapeutic agents for this disease.
- Published
- 2005
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18. [A case report of systemic capillary leak syndrome. Effective treatment with immunoadsorption and leukotriene antagonist].
- Author
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Wålinder O, Einarsson P, and Lindberger K
- Subjects
- Acetates therapeutic use, Adult, Blood Proteins, Capillary Leak Syndrome drug therapy, Capillary Leak Syndrome immunology, Cyclopropanes, Female, Humans, Immunosorbent Techniques, Leukotriene Antagonists therapeutic use, Quinolines therapeutic use, Sulfides, Treatment Outcome, Capillary Leak Syndrome therapy
- Abstract
Systemic capillary leak syndrome (SCLS) is an unusual condition characterized by periodic leakage of plasma proteins through the capillary wall, leading to hypoalbuminaemia, hypovolaemia, haemoconcentration and shock. The pathogenesis is unknown and the mortality high. Various prophylactic treatments have been tried but are difficult to evaluate because of the unpredictable course of the disease. We describe one patient with frequent attacks of SCLS, that did not respond to any kind of treatment regimens over a period of nine years. Subsequently, therapy with regular immunoadsorption of plasma proteins and a leukotriene receptor antagonist was attempted. This treatment has now been given for six years and only one episode of capillary leakage has occurred. The effect may be due to removal of pathogenic immunoglobulins or immune complexes and/or inhibition of leukotriene-induced capillary leakage.
- Published
- 2004
19. IL-4 exacerbates anaphylaxis.
- Author
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Strait RT, Morris SC, Smiley K, Urban JF Jr, and Finkelman FD
- Subjects
- Adjuvants, Immunologic adverse effects, Adjuvants, Immunologic antagonists & inhibitors, Adjuvants, Immunologic biosynthesis, Adjuvants, Immunologic physiology, Anaphylaxis pathology, Anaphylaxis physiopathology, Anaphylaxis prevention & control, Animals, Capillary Leak Syndrome blood, Capillary Leak Syndrome immunology, Capillary Leak Syndrome physiopathology, Dose-Response Relationship, Immunologic, Drug Therapy, Combination, Female, Injections, Intravenous, Interleukin-12 administration & dosage, Interleukin-12 therapeutic use, Interleukin-13 adverse effects, Interleukin-13 physiology, Interleukin-18 administration & dosage, Interleukin-18 therapeutic use, Interleukin-4 antagonists & inhibitors, Interleukin-4 biosynthesis, Leukotriene C4 administration & dosage, Male, Mice, Mice, Inbred BALB C, Mice, Knockout, Mice, Nude, Mice, Transgenic, Platelet Activating Factor administration & dosage, STAT6 Transcription Factor, Serotonin administration & dosage, Signal Transduction immunology, Trans-Activators physiology, Anaphylaxis immunology, Interleukin-4 adverse effects, Interleukin-4 physiology
- Abstract
We evaluated whether IL-4, a cytokine critical for inducing allergic responses, also contributes to the effector phase of allergy. Pretreatment of mice with IL-4 or the related cytokine, IL-13, rapidly and dramatically increased the severity of anaphylaxis induced by cross-linking Fc(epsilon)RI or FcgammaRIII. This effect was inhibited by endogenously produced IFN-gamma, was T cell-, B cell-, and common gamma-chain-independent, and required IL-4Ralpha and Stat6. IL-4Ralpha signaling also enhanced anaphylaxis in mice infected with a nematode parasite that stimulates IL-4/IL-13 production. IL-4 exacerbated anaphylaxis by acting synergistically with vasoactive mediators to increase vascular permeability. Synergy between IL-4 and vasoactive mediators during the effector phase of allergic inflammation may both contribute to allergic immunopathology and enhance protective immunity against gastrointestinal worms.
- Published
- 2003
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20. Toxigenic Helicobacter pylori induces changes in the gastric mucosal microcirculation in rats.
- Author
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Kalia N, Bardhan KD, Atherton JC, and Brown NJ
- Subjects
- Animals, Capillaries pathology, Capillary Leak Syndrome immunology, Capillary Leak Syndrome pathology, Gastric Mucosa immunology, Gastric Mucosa microbiology, Helicobacter pylori genetics, Image Processing, Computer-Assisted, In Situ Hybridization, Fluorescence methods, Lymphocyte Activation, Male, Platelet Activation, Rats, Rats, Wistar, Statistics, Nonparametric, Venules pathology, Capillary Leak Syndrome microbiology, Gastric Mucosa blood supply, Helicobacter pylori pathogenicity
- Abstract
Background and Aims: One of the key components of inflammation is changes in vascular structure and function. This suggests that the microcirculation may be a key target of Helicobacter pylori released factors. It has previously been shown in vivo that pooled H pylori extracts from duodenal ulcer/gastritis patients induce platelet aggregation but no leucocyte activation within rat gastric mucosal microcirculation (GMMC). However, infection with strains associated with ulcer disease as compared with gastritis may exert greater effects on the microcirculation. This study used fluorescent in vivo microscopy to determine the acute effects of extracts of genotypically different H pylori strains on the GMMC., Methods: Three H pylori extracts, with different cagA and VacA toxigenic status, were individually administered to the gastric mucosa of anaesthetised Wistar rats. The mucosal surface was visualised via an incision made in the exteriorised stomach. Fluoroscein isothiocyanate conjugated to bovine serum albumin (FITC-BSA) or acridine orange was used to quantify macromolecular leak (MML) and leucocyte/platelet activity respectively for 120 minutes. Changes in capillary and post-capillary venule (PCV) diameters were also monitored., Results: The cagA(+) VacA toxigenic strain 60190 induced significant and sustained MML by five minutes (p<0.01). Transient and less leakage was observed with its isogenic VacA(-) mutant and other non-toxigenic strains regardless of cagA status. Significant increases in leucocyte adhesion (p<0.05), platelet aggregation (p<0.05), and PCV vasoconstriction (p<0.05) were only observed with the cag A(+) and toxigenic strain., Conclusion: Extracts of H pylori are capable of inducing marked disturbances within the rat GMMC. These disturbances seem to be dependent on the production of an active vacuolating cytotoxin. Varying effects on the GMMC may explain the clinically diverse outcomes associated with genotypically different strains.
- Published
- 2002
- Full Text
- View/download PDF
21. [Systemic capillary leak syndrome associated with lymphoproliferative disease].
- Author
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Puig Ponsico G, Cortada P, Celma A, and Arderiu A
- Subjects
- Bronchodilator Agents therapeutic use, Capillary Leak Syndrome drug therapy, Capillary Leak Syndrome immunology, Humans, Immunoglobulin G blood, Immunoglobulin G immunology, Male, Middle Aged, Terbutaline therapeutic use, Theophylline therapeutic use, Capillary Leak Syndrome etiology, Lymphoproliferative Disorders complications
- Published
- 2002
- Full Text
- View/download PDF
22. C1 inhibitor prevents capillary leakage after thermal trauma.
- Author
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Radke A, Mottaghy K, Goldmann C, Khorram-Sefat R, Kovacs B, Janssen A, Klosterhalfen B, Hafemann B, Pallua N, and Kirschfink M
- Subjects
- Animals, Bacterial Translocation drug effects, Bacterial Translocation immunology, Burns pathology, Capillary Leak Syndrome pathology, Complement Activation drug effects, Complement Activation immunology, Kidney pathology, Liver pathology, Lung pathology, Prospective Studies, Skin pathology, Swine, Burns immunology, Capillary Leak Syndrome immunology, Complement C1 Inactivator Proteins pharmacology
- Abstract
Objective: In burned patients, activation of the complement and clotting systems is suggested to play an important role in the development of the capillary leak syndrome and inflammatory tissue destruction. In an animal model of thermal trauma, the possible protective effect of C1 inhibitor (C1Inh), a major control protein of both the complement and clotting systems, was investigated., Design: Prospective, controlled study., Setting: Animal model., Subjects: Healthy pigs weighing 30 kg., Interventions: Pigs were scalded for 25 secs with 75 degrees C hot water to achieve a 30% total body surface deep partial-thickness burn. The treatment group (n = 8) received C1Inh concentrate at an initial dose of 100 units/kg body weight immediately after thermal trauma, followed by three further applications every 12 hrs. Two control groups included animals that were either scalded (n = 8) or not scalded (n = 7) and treated with lactated Ringer's solution., Measurements: Before and at various time points after trauma blood samples were analyzed for complement activation (APH50, CH50, SC5b-9, C3). Continuous monitoring of hemodynamic variables was performed and postmortem histologic examination of specimens from lung, heart, liver, kidney, stomach, duodenum, jejunum, ileum, and colon was carried out. Aseptically collected mesenteric lymph nodes were pooled and screened for bacterial translocation. For evaluation of the burn wound, biopsies from defined scalded and not scalded areas were taken daily. As a measure for edema formation, the weight of the animals was recorded every 2 hrs., Results: After C1Inh treatment, which led to a significantly reduced complement activation, the clinical outcome was clearly improved, as indicated by vital signs and as demonstrated by reduced edema formation. Treated animals presented a diminished bacterial translocation. Pathologic alterations were clearly diminished in the burned skin, in shock-related organs, and in the intestines., Conclusion: Application of C1Inh appears to be an effective means to prevent capillary leakage and inflammatory tissue destruction after thermal trauma.
- Published
- 2000
- Full Text
- View/download PDF
23. Lethal capillary leak syndrome after a single administration of interferon beta-1b.
- Author
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Niederwieser G
- Subjects
- Capillary Leak Syndrome immunology, Diagnosis, Differential, Humans, Interferon beta-1a, Interferon beta-1b, Multiple Sclerosis diagnosis, Multiple Sclerosis drug therapy, Multiple Sclerosis immunology, Paraproteinemias diagnosis, Paraproteinemias immunology, Adjuvants, Immunologic adverse effects, Capillary Leak Syndrome chemically induced, Interferon-beta adverse effects
- Published
- 2000
- Full Text
- View/download PDF
24. [Immunonutrition with omega-3-fatty acids. Are new anti-inflammatory strategies in sight?].
- Author
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Heller A and Koch T
- Subjects
- Animals, Capillary Leak Syndrome immunology, Capillary Leak Syndrome therapy, Critical Care, Humans, Inflammation Mediators blood, Systemic Inflammatory Response Syndrome immunology, Treatment Outcome, Fatty Acids, Omega-3 administration & dosage, Systemic Inflammatory Response Syndrome therapy
- Abstract
In the early phase of sepsis and SIRS an overwhelming activation of humoral and cellular mediator systems can alter vascular resistance and causes capillary leakage increasing the risk of organ dysfunction. omega-6-arachidonic acid is released from lipid pools of cellular membranes during inflammation and is metabolized to pro-inflammatory prostaglandins and leukotriens, which are key mediators in the pathogenesis of organ dysfunction. omega-3-eicosapentaenoic acid-derived lipid mediators present altered biologic effects. Thus, omega-3-fatty acid application enables anti-inflammatory intervention on the level of lipid mediators. The current article reviews experimental and clinical data on omega-3-fatty acids. Besides the decrease of pro-inflammatory mediators, fish oil supplementation lowered post operative infection rates and showed a tendency to reduce hospital stay in surgical patients. It is believed that the decreased formation of LTB4 and TXA2 during sepsis after administration of omega-3-fatty acids accounts for improved microcirculatory perfusion and declined lactate acidosis.
- Published
- 2000
25. Evidence for the involvement of CD44 in endothelial cell injury and induction of vascular leak syndrome by IL-2.
- Author
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Rafi-Janajreh AQ, Chen D, Schmits R, Mak TW, Grayson RL, Sponenberg DP, Nagarkatti M, and Nagarkatti PS
- Subjects
- Adoptive Transfer, Animals, Antibodies, Monoclonal administration & dosage, B-Lymphocytes drug effects, B-Lymphocytes immunology, Capillary Leak Syndrome etiology, Capillary Leak Syndrome genetics, Capillary Leak Syndrome pathology, Cells, Cultured, Cytotoxicity, Immunologic genetics, Endothelium, Vascular chemistry, Female, Hyaluronan Receptors administration & dosage, Hyaluronan Receptors biosynthesis, Hyaluronan Receptors genetics, Hyaluronic Acid pharmacology, Immunoglobulin Fab Fragments administration & dosage, Injections, Intraperitoneal, Interleukin-2 administration & dosage, Killer Cells, Lymphokine-Activated immunology, Liver pathology, Liver ultrastructure, Lung pathology, Lung ultrastructure, Lymphocyte Activation drug effects, Lymphocyte Activation genetics, Mice, Mice, Inbred C57BL, Mice, Knockout, Spleen cytology, Spleen transplantation, Tumor Cells, Cultured, Capillary Leak Syndrome immunology, Endothelium, Vascular immunology, Endothelium, Vascular pathology, Hyaluronan Receptors immunology
- Abstract
At sites of chronic inflammation seen during infections, autoimmunity, graft-vs-host response, and cytokine therapy, endothelial cell injury is known to occur, the exact mechanism of which is unknown. In the current study we used IL-2-induced vascular leak syndrome (VLS) as a model to investigate whether cytotoxic lymphocytes use CD44 in mediating endothelial cell injury. Administration of IL-2 to wild-type mice triggered significant VLS in the lungs and liver. In contrast, in CD44 knockout (KO) mice, IL-2-induced VLS was markedly reduced in the lungs and liver. IL-2-treated wild-type and CD44 KO mice had similar levels of perivascular infiltration with lymphocytes in the lungs and liver. This suggested that the decrease in VLS seen in CD44 KO mice was not due to the inability of lymphocytes to migrate to these organs. Ultrastructural studies demonstrated extensive endothelial cell damage in the lungs and liver of IL-2-treated wild-type, but not CD44 KO, mice. Moreover, CD44-KO mice exhibited a marked decrease in IL-2-induced lymphokine-activated killer cell activity. The induction of VLS was dependent on the expression of CD44 on immune cells rather than endothelial cells because adoptive transfer of CD44+, but not CD44- spleen cells along with IL-2 into CD44 KO mice triggered VLS. The IL-2-induced VLS was blocked by administration of F(ab')2 of Abs against CD44. The current study demonstrates that CD44 plays a key role in endothelial cell injury. Blocking CD44 in vivo may offer a novel therapeutic approach to prevent endothelial cell injury by cytotoxic lymphocytes in a variety of clinical disease models.
- Published
- 1999
26. Tolerability and side effects of anti-CD3-immunotoxin in preclinical testing in kidney and pancreatic islet transplant recipients.
- Author
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Contreras JL, Eckhoff DE, Cartner S, Frenette L, Thomas FT, Robbin ML, Neville DM Jr, and Thomas JM
- Subjects
- Animals, Capillary Leak Syndrome etiology, Capillary Leak Syndrome immunology, Chemical and Drug Induced Liver Injury, Cyclosporine administration & dosage, Immune Tolerance, Immunotoxins adverse effects, Kidney Function Tests, Liver Function Tests, Macaca mulatta, Male, Methylprednisolone administration & dosage, Transplantation Conditioning, CD3 Complex immunology, Islets of Langerhans Transplantation, Kidney Transplantation
- Abstract
Introduction: Anti-CD3-immunotoxin (alpha-CD3-IT) promotes allograft tolerance in nonhuman primates owing to efficient depletion of sessile and circulating T cells. Common side effects of vascular leak syndrome, hepatotoxicity, and nephrotoxicity have limited tolerability of other immunotoxins. We report on preclinical studies of alpha-CD3-IT-related side effects., Methods: Normal rhesus monkeys received a kidney transplant and alpha-CD3-IT alone (on day -to +2) or in combination with brief peritransplant adjunctive immunosuppressive therapy. Some received donor CD34+ cells. Blood chemistries, complete blood count, weight, liver, and kidney biopsies were examined for immunotoxin-related changes. Five spontaneously diabetic primates also received alpha-CD3-IT, three of whom had a pancreas islet transplant., Results: The main side effect of alpha-CD3-IT, vascular leak syndrome, was entirely prevented by adjunctive immunosuppressive therapy. Renal and liver function tests and biopsies revealed a lack of nephrotoxicity and hepatotoxicity. All had transient weight loss (14+/-5%). Without infusion of donor CD34+ cells, 97% had full weight recovery. Of those given donor CD34+ cells, 50% were euthanized for wasting., Conclusions: Side effects of alpha-CD3-IT are manageable and should not prevent therapeutic application.
- Published
- 1999
- Full Text
- View/download PDF
27. Intrapulmonary protein leakage in immunocompromised children and adults with pneumonia.
- Author
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Ratjen F, Havers W, and Braun J
- Subjects
- Adolescent, Adult, Biomarkers, Capillary Leak Syndrome immunology, Child, Child, Preschool, Hematologic Neoplasms complications, Hematologic Neoplasms therapy, Humans, Middle Aged, Pneumonia immunology, Statistics, Nonparametric, Blood Proteins analysis, Bronchoalveolar Lavage Fluid chemistry, Capillary Leak Syndrome complications, Immunosuppression Therapy, Pneumonia complications
- Abstract
Background: Pulmonary infections are associated with an increase in capillary permeability but information regarding age related differences in the local inflammatory response is lacking. To quantify the degree of capillary leakage during inflammation, the concentrations of the plasma proteins albumin, alpha1-antitrypsin, alpha2-macroglobulin and the locally produced proteins elastase, myeloperoxidase, lactoferrin and fibronectin were studied in the bronchoalveolar lavage (BAL) fluid of immunosuppressed children and adults with pneumonia., Methods: Sixteen children aged 2-16 years and 15 adults who developed pneumonia while receiving immunosuppressive therapy for haematological malignancies were included in the study. Bronchoalveolar lavage was performed via a flexible bronchoscope with three aliquots of 1 ml/kg body weight in children and 200 ml in adults. Protein concentrations in BAL fluid were determined using highly sensitive immunoluminometric assays., Results: Despite considerable variability, the median concentrations of all proteins in BAL fluid were significantly higher in both patient populations than in previously collected age adjusted reference values. The concentrations of serum derived proteins were significantly higher in children with pneumonia than in adult patients. In contrast, no differences were observed between the two groups for locally produced proteins., Conclusions: These data suggest that the degree of protein exudation is more pronounced in immunosuppressed children with pneumonia than in adults in a similar clinical situation. This is in agreement with our studies in healthy individuals and may reflect a greater permeability of the alveolar-capillary membrane in children, regardless of disease status.
- Published
- 1999
- Full Text
- View/download PDF
28. Immunopathogenesis of Dengue hemorrhagic fever.
- Author
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Rothman AL and Ennis FA
- Subjects
- Antibodies, Viral, Capillary Leak Syndrome complications, Cross Reactions, Cytokines biosynthesis, Dengue Virus immunology, Humans, Lymphocyte Activation, Models, Immunological, Monocytes immunology, Serotyping, Severe Dengue complications, T-Lymphocytes immunology, Capillary Leak Syndrome immunology, Severe Dengue immunology
- Published
- 1999
- Full Text
- View/download PDF
29. Complement activation, cytokines, and adhesion molecules in children undergoing cardiac surgery with or without cardiopulmonary bypass.
- Author
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Tárnok A, Hambsch J, Emmrich F, Sack U, van Son J, Bellinghausen W, Borte M, and Schneider P
- Subjects
- Adolescent, Capillary Leak Syndrome diagnosis, Capillary Leak Syndrome immunology, Child, Child, Preschool, E-Selectin blood, Female, Heart Defects, Congenital immunology, Humans, Intercellular Adhesion Molecule-1 blood, Interleukin-6 blood, Interleukin-8 blood, Male, Multiple Organ Failure diagnosis, Multiple Organ Failure immunology, Postoperative Complications diagnosis, Prospective Studies, Risk Factors, Systemic Inflammatory Response Syndrome diagnosis, Cardiopulmonary Bypass, Cell Adhesion Molecules blood, Complement Activation immunology, Cytokines blood, Heart Defects, Congenital surgery, Postoperative Complications immunology, Systemic Inflammatory Response Syndrome immunology
- Abstract
The effect of cardiopulmonary bypass (CPB) on various blood parameters in children undergoing major cardiovascular surgery was investigated in a prospective clinical study. Blood samples of children with CPB (CPB group, n = 18) or without CPB (control, n = 12) were collected before, during, and after surgery. The concentration of routine laboratory parameters, components of the complement system (C3, C4, C5, C1 inhibitor, total hemolytic complement, C3d, and C5a), circulating interleukins (IL-6 and IL-8) and soluble adhesion molecules (sICAM-1 and sE-selectin) were determined. In both groups of patients the serum concentrations of C3, C4, C5, and C1 inhibitor were significantly affected by the treatments (p < 0.001), decreased immediately after onset of anesthesia, were minimal during surgery, and increased thereafter. No significant differences in the kinetics of these parameters were detectable between CPB and control group. In the CPB group the activation of the alternative pathway (increased C3d) was found to be a specific response (p = 0.005), but also in the control group C3d and C5a concentration increased significantly (p < 0.022), indicating complement activation. None of the effects that would be expected after activation of the complement system were specific for the CPB group. In both groups the serum levels of IL-6 increased dramatically during and/or after surgery (p = 0.001), and IL-8 was detectable after surgery in 10/12 control patients. The concentration of sICAM-1 and sE-selectin decreased during surgery (p < 0.04) and later did not increase above baseline. Our data suggest that increased serum levels of inflammation mediators and increased consumption of complement and adhesion molecules occur during cardiovascular surgery. Although complement activation and ICAM-1 consumption are more pronounced in the CPB patients, none of these changes occurs exclusively in the CPB group. We conclude, therefore, that these changes are the combined effect of anesthesia, surgical trauma, and endothelial lesions. Additional, undefined CPB-induced reactions may also contribute the postoperative morbidity.
- Published
- 1999
- Full Text
- View/download PDF
30. Systemic capillary leak syndrome.
- Author
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Beermann W, Hörstrup KA, and Will R
- Subjects
- Aged, Antineoplastic Agents therapeutic use, Capillary Leak Syndrome immunology, Capillary Leak Syndrome therapy, Humans, Male, Multiple Myeloma drug therapy, Paraproteins metabolism, Capillary Leak Syndrome etiology, Multiple Myeloma complications, Paraproteinemias complications
- Published
- 1998
- Full Text
- View/download PDF
31. Complement activation in relation to capillary leakage in children with septic shock and purpura.
- Author
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Hazelzet JA, de Groot R, van Mierlo G, Joosten KF, van der Voort E, Eerenberg A, Suur MH, Hop WC, and Hack CE
- Subjects
- Adolescent, Capillary Leak Syndrome mortality, Capillary Leak Syndrome pathology, Child, Child, Preschool, Female, Humans, Infant, Inflammation immunology, Inflammation pathology, Male, Meningococcal Infections mortality, Meningococcal Infections pathology, Neisseria meningitidis, Purpura mortality, Purpura pathology, Shock, Septic mortality, Shock, Septic pathology, Survival Rate, Capillary Leak Syndrome immunology, Complement Activation immunology, Meningococcal Infections immunology, Purpura immunology, Shock, Septic immunology
- Abstract
To assess the relationship between capillary leakage and inflammatory mediators during sepsis, blood samples were taken on hospital admission, as well as 24 and 72 h later, from 52 children (median age, 3.3 years) with severe meningococcal sepsis, of whom 38 survived and 14 died. Parameters related to cytokines (interleukin 6 [IL-6] IL-8, plasma phospholipase A2, and C-reactive protein [CRP]), to neutrophil degranulation (elastase and lactoferrin), to complement activation (C3a, C3b/c, C4b/c, and C3- and C4-CRP complexes), and to complement regulation (functional and inactivated C1 inhibitor and C4BP) were determined. The degree of capillary leakage was derived from the amount of plasma infused and the severity of disease by assessing the pediatric risk of mortality (PRISM) score. Levels of IL-6, IL-8, C3b/c, C3-CRP complexes, and C4BP on admission, adjusted for the duration of skin lesions, were significantly different in survivors and nonsurvivors (C3b/c levels were on average 2.2 times higher in nonsurvivors, and C3-CRP levels were 1.9 times higher in survivors). Mortality was independently related to the levels of C3b/c and C3-CRP complexes. In agreement with this, levels of complement activation products correlated well with the PRISM score or capillary leakage. Thus, these data show that complement activation in patients with severe meningococcal sepsis is associated with a poor outcome and a more severe disease course. Further studies should reveal whether complement activation may be a target for therapeutical intervention in this disease.
- Published
- 1998
- Full Text
- View/download PDF
32. Evidence for the involvement of Fas ligand and perforin in the induction of vascular leak syndrome.
- Author
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Rafi AQ, Zeytun A, Bradley MJ, Sponenberg DP, Grayson RL, Nagarkatti M, and Nagarkatti PS
- Subjects
- Animals, CD4-Positive T-Lymphocytes drug effects, CD8-Positive T-Lymphocytes drug effects, Capillary Leak Syndrome immunology, Capillary Leak Syndrome pathology, Capillary Leak Syndrome physiopathology, Capillary Permeability immunology, Cell Line, Transformed, Cytotoxicity, Immunologic, Disease Models, Animal, Endothelium, Vascular pathology, Endothelium, Vascular physiopathology, Endothelium, Vascular ultrastructure, Fas Ligand Protein, Female, Hyaluronan Receptors biosynthesis, Injections, Intraperitoneal, Interleukin-2 administration & dosage, Interleukin-2 pharmacology, Killer Cells, Lymphokine-Activated immunology, Killer Cells, Lymphokine-Activated metabolism, Ligands, Liver blood supply, Liver pathology, Lung blood supply, Lung pathology, Lymphocyte Count drug effects, Membrane Glycoproteins deficiency, Membrane Glycoproteins genetics, Mice, Mice, Inbred C57BL, Mice, Inbred MRL lpr, Mice, Knockout, Perforin, Pore Forming Cytotoxic Proteins, Tumor Cells, Cultured, fas Receptor genetics, Capillary Leak Syndrome etiology, Membrane Glycoproteins physiology, fas Receptor metabolism
- Abstract
Endothelial cell injury resulting in vascular leak syndrome (VLS) is one of the most widely noted phenomenons in a variety of clinical diseases. In the current study we used IL-2-induced VLS as a model to investigate the role of cytolytic lymphocytes in the cytotoxicity of endothelial cells. Administration of IL-2 (75,000 U/mouse, three times a day for 3 days) into BL/6 wild-type mice triggered significant VLS in the lungs, liver, and spleen. Interestingly, perforin-knockout (KO) mice exhibited a marked decrease in IL-2-induced VLS in all three organs tested. Also, Fas ligand-defective (gld) mice and Fas-deficient (lpr) mice exhibited decreased VLS in the liver and spleen, but not in the lungs. The decreased VLS seen in perforin-KO, gld, and lpr mice was not due to any defect in lymphocyte migration or homing to various organs because histopathologic studies in these mice demonstrated significant and often greater perivascular infiltration of lymphocytes compared with the IL-2-treated wild-type mice. Ultrastructural studies of the lungs demonstrated significant damage to the endothelial cells in IL-2-treated wild-type mice and decreased damage in perforin-KO mice. IL-2 administration caused up-regulation of CD44 in all strains of mice tested and triggered increased LAK activity against an endothelial cell line in wild-type and gld mice, but not in perforin-KO mice. The current study demonstrates for the first time that perforin and Fas ligand may actively participate in endothelial cell injury and induction of VLS in a variety of organs.
- Published
- 1998
33. Idiopathic capillary leak syndrome: evidence of CD8-positive lymphocytes surrounding damaged endothelial cells.
- Author
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Cicardi M, Berti E, Caputo V, Radice F, Gardinali M, and Agostoni A
- Subjects
- Antigens, CD1 immunology, CD3 Complex analysis, CD8 Antigens analysis, Female, Humans, Lymphocyte Count, Middle Aged, Receptors, Interleukin-2 immunology, CD8-Positive T-Lymphocytes immunology, Capillary Leak Syndrome immunology, Capillary Leak Syndrome pathology, Endothelium pathology, Skin pathology
- Published
- 1997
- Full Text
- View/download PDF
34. Generation of the complement activation product C5a precedes interleukin-2-induced capillary leakage syndrome.
- Author
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Nurnberger W, Holthausen S, Michelmann I, Jurgens H, Burdach S, and Gobel U
- Subjects
- Adolescent, Antineoplastic Agents therapeutic use, Capillary Leak Syndrome immunology, Child, Humans, Infusions, Intravenous, Interleukin-2 therapeutic use, Recombinant Proteins adverse effects, Recombinant Proteins therapeutic use, Antineoplastic Agents adverse effects, Capillary Leak Syndrome etiology, Complement C5a biosynthesis, Complement Pathway, Classical drug effects, Interleukin-2 adverse effects
- Abstract
Capillary leakage syndrome (CLS) is a severe side effect of intravenous interleukin-2 (IL-2) therapy. Twenty-seven cycles of IL-2 therapy [six (day 1), nine (day 2), and 12 >( 10(6) U/m(2) body surface (days 3 to 5), given as continuous infusion] were analyzed in children and adolescents. The anaphylatoxin C5a was assessed as an early predictor for CLS. CLS developed in 11 of 27 cycles of IL-2 infusion. C5a at day 2 of IL-2 infusion (0.8-9.43 mu g/L; median, 1.8 mu g/L) was increased in CLS patients when compared with baseline values (0.21-0.74 mu g/L; median, 0.40 mu g/L; p = 0.01) and when compared with C5a at day 2 in non-CLS patients (0.44-1.2 mu g/L; median, 0.62 mu g/L; p <0.01). Ten of 11 CLS patients showed C5a levels >1.0 mu g/L, whereas 14 of 16 patients who did not develop CLS showed C5a <1.0 mu g/L (predictive value positive 83% for CLS).
- Published
- 1996
- Full Text
- View/download PDF
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