Leukocyte phenotyping to stratify septic shock patients
ABSTRACT In a recent study conducted in a cohort of 52 septic patients, Monserrat and coworkers found that profound failure of peripheral T cells to convert from a naïve phenotype to an activated phenotype has positive predictive value in identifying patients who do not recover. These data support the hypothesis that failure of the innate immune system to engage the T-cell compartment contributes to sepsis mortality and provides motivation for the development and clinical evaluation of immunostimulatory therapies for patients with sepsis.
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ABSTRACT: The study by Souza-Fonseca-Guimaraes and colleagues in the previous issue of Critical Care shows several alterations in blood natural killer (NK) characteristics during human sepsis and systemic inflammatory response syndrome, including changes in NK cell numbers, Toll-like receptor (TLR) expression, and responsiveness to TLR agonists. This paper advances our knowledge of NK cell biology during sepsis and provides the background for future investigations.Critical care (London, England) 12/2012; 16(6):185. DOI:10.1186/cc11881
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ABSTRACT: Sepsis is a systemic inflammatory response syndrome due to infection. The incidence rate is estimated to be up to 19 million cases worldwide per year and the number of cases is rising. Infection triggers a complex and prolonged host response, in which both the innate and adaptive immune response are involved. The disturbance of immune system cells plays a key role in the induction of abnormal levels of immunoregulatory molecules. Furthermore, the involvement of effector immune system cells also impairs the host response to the infective agents and tissue damage. Recently, postmortem studies of patients who died of sepsis have provided important insights into why septic patients die and showed an extensive depletion of CD4 and CD8 lymphocytes and they found that circulating blood cells showed similar findings. Thus, the knowledge of the characterization of circulating lymphocyte abnormalities is relevant for the understanding of the sepsis pathophysiology. In addition, monitoring the immune response in sepsis, including circulating lymphocyte subsets count, appears to be potential biomarker for predicting the clinical outcome of the patient. This paper analyzes the lymphocyte involvement and dysfunction found in patients with sepsis and new opportunities to prevent sepsis and guide therapeutic intervention have been revealed.BioMed Research International 08/2014; 2014:671087. DOI:10.1155/2014/671087 · 2.71 Impact Factor
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ABSTRACT: Patients with critical illness, and in particular sepsis, are now recognized to undergo unifying, pathogenic, disturbances of immune function. Whilst scientific and therapeutic focus has traditionally been on understanding and modulating the initial pro-inflammatory limb, recent years have witnessed a re-focusing on the development and importance of immunosuppressive 'anti-inflammatory' pathways. Several mechanisms are known to drive this phenomenon, however no over-riding conceptual framework justifies them. In this article we review the contribution of pro-resolution pathways to this phenotype, describing the observed immune alterations in terms of either a failure of resolution of inflammation or the persistence of pro-resolution processes causing inappropriate 'injurious resolution'; a novel hypothesis. The dysregulation of key processes in critical illness including apoptosis of infiltrating neutrophils and their efferocytosis by macrophages are discussed along with the emerging role of specialized cell subtypes Gr1+CD11b+ myeloid-derived suppressor cells and CD4+CD25+Fox3p+ T-regulatory cells.The Journal of Pathology 09/2013; 231(1). DOI:10.1002/path.4232 · 7.33 Impact Factor