Release of Danger-Associated Molecular Patterns following Chemotherapy Does Not Induce Immunoparalysis in Leukemia Patients.

Chemotherapy may result in the release of danger-associated molecular patterns (DAMPs), which can cause immunoparalysis (deactivation of the immune system). We investigated DAMPs following chemotherapy and their relationship with markers of immunoparalysis in leukemia patients. In 6 patients with acute myeloid leukemia or myelodysplastic syndrome and 12 healthy subjects, DAMPs, cytokines, and markers of immunoparalysis were determined before and during the first week after chemotherapy initiation.

Mitochondrial DNA and TLR9 Signaling Is Not Involved in Mechanical Ventilation-Induced Inflammation.

Exogenous administration of mitochondrial DNA (mtDNA) causes inflammatory lung injury in a toll-like receptor (TLR) 9-dependent manner. We investigated whether mechanical ventilation results in endogenous release of mtDNA and whether TLR9 plays a role in the pulmonary inflammatory response induced by mechanical ventilation.Wild-type and TLR9/ C57bl/6 mice were ventilated with low (8 mL/kg) and high (32 mL/kg) tidal volumes for 4 hours.

Plasma levels of danger-associated molecular patterns are associated with immune suppression in trauma patients.

Purpose: Danger-associated molecular patterns (DAMPs) released of trauma could contribute to an immune suppressed state that renders patients vulnerable towards nosocomial infections. We investigated DAMP release in trauma patients, starting in the prehospital phase, and assessed its relationship with immune suppression and nosocomial infections.

Methods: Blood was obtained from 166 adult trauma patients at the trauma scene, emergency room (ER), and serially afterwards.

Plasma Nuclear and Mitochondrial DNA Levels, and Markers of Inflammation, Shock, and Organ Damage in Patients with Septic Shock.

Background: Plasma levels of the danger-associated molecular patterns (DAMPs) nuclear DNA (nDNA) and mitochondrial DNA (mtDNA) have been shown to be related to sepsis mortality. However, the intermediate factors and/or mechanisms contributing to this relation are largely unknown. Our aim was to determine whether plasma levels of nDNA and mtDNA are related to the markers of inflammation, severity of shock, and organ damage in septic shock patients.

DANGER IN THE INTENSIVE CARE UNIT: DAMPS IN CRITICALLY ILL PATIENTS.

Danger-associated molecular patterns (DAMPs) that are released by injured, threatened, or dead cells, or that originate from the extracellular matrix, influence the immune system. This is of great relevance in critically ill patients, in whom trauma or surgery-related cell damage, hypoxia, ischemia, and infections can result in extensive release of DAMPs. As many patients at the intensive care unit suffer from immune system-related complications, DAMPs could serve as markers for the prognosis of these patients and represent possible therapeutic targets.

The Involvement of Danger-Associated Molecular Patterns in the Development of Immunoparalysis in Cardiac Arrest Patients.

Objectives: After cardiac arrest, patients are highly vulnerable toward infections, possibly due to a suppressed state of the immune system called "immunoparalysis." We investigated if immunoparalysis develops following cardiac arrest and whether the release of danger-associated molecular patterns could be involved.

Design: Observational study.

Soluble urokinase-type plasminogen activator levels are related to plasma cytokine levels but have low predictive value for mortality in trauma patients.

Introduction: Soluble urokinase-type plasminogen activator (suPAR) represents a marker for immune activation and has predictive value in critically ill patients. The kinetics of suPAR and its correlation with the immune response and outcome in trauma patients are unknown.

Methods: Plasma concentrations of inflammatory cytokines and suPAR were determined in adult trauma patient (n = 69) samples obtained by the Helicopter Emergency Medical Services at arrival at the emergency department (ED) and at days 1, 3, 5, 7, 10, and 14.

Circulating iFABP Levels as a marker of intestinal damage in trauma patients.

Both the initial trauma and the subsequent hemodynamic instability may contribute to intestinal damage, which is of great importance in (immunological) posttrauma complications. This study assesses intestinal damage using the biomarker intestinal Fatty Acid Binding Protein (iFABP) in trauma patients during the first days of their hospital admission and the risk factors involved. Plasma iFABP levels were measured in blood samples obtained from adult multiple trauma patients (n = 93) at the trauma scene by the Helicopter Emergency Medical Services, at arrival at the emergency department (ED), and at days 1, 3, 5, 7, 10, and 14 after trauma and related to injury severity and hemodynamic parameters.

Distinct phenotypes of cardiac allograft vasculopathy after heart transplantation: a histopathological study.

Introduction: Long-term survival after heart transplantation (HTx) is hampered by cardiac allograft vasculopathy (CAV). Better understanding of the pathophysiological mechanisms of CAV might have considerable consequences for therapeutic approaches in the future. The aim of the present study was to investigate the histological phenotypes of CAV in relation with clinical patient characteristics.

Blueprints of signaling interactions between pattern recognition receptors: implications for the design of vaccine adjuvants.

Innate immunity activation largely depends on recognition of microorganism structures by Pattern Recognition Receptors (PRRs). PRR downstream signaling results in production of pro- and anti-inflammatory cytokines and other mediators. Moreover, PRR engagement in antigen-presenting cells initiates the activation of adaptive immunity.

The anti-CD20 antibody rituximab reduces the Th17 cell response.

Objective: Rituximab has been shown to be successful in the treatment of rheumatoid arthritis (RA), and this unexpected finding indicates that B cells have an important role in this disease. The present study was undertaken to investigate the mechanism of action of rituximab in RA.

Methods: Twelve patients with active RA were treated with rituximab.

The calcium-sensing receptor promotes urinary acidification to prevent nephrolithiasis.

Hypercalciuria increases the risk for urolithiasis, but renal adaptive mechanisms reduce this risk. For example, transient receptor potential vanilloid 5 knockout (TPRV5(-/-)) mice lack kidney stones despite urinary calcium (Ca(2+)) wasting and hyperphosphaturia, perhaps as a result of their significant polyuria and urinary acidification. Here, we investigated the mechanisms linking hypercalciuria with these adaptive mechanisms.