Cellular and Molecular Markers of Outcome in Septic Shock

Sepsis can be defined as a generalized inflammatory response that occurs during infection (Bone et al. 1992) and it seems that a defective host immune system response to a microbiological challenge is pivotal in the pathogenesis of septic shock. The pathogenesis of sepsis is a result of a complex network of events involving inflammatory and antiinflammatory processes, molecular and cellular reactions and circulatory abnormalities (Hotchkiss & Karl 2003). Signs and symptoms of sepsis are non-specific for the diagnosis of sepsis, but early and appropriate intervention is critical for morbidity and mortality (Levy et al. 2005;Rivers et al. 2001). There is a need to find early markers of infection in patients with systemic inflammatory response syndrome (SIRS), and also to establish procedures for a more accurate risk assessment, predicting patients’ outcome, guiding antibiotic therapy or predicting the development of different organ dysfunctions. A biomarker is defined as “a characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes or pharmacologic responses to a therapeutic intervention”(Biomarkers 2001). Countless biomarkers of septic shock have been proposed but few or none are currently used in clinical practice or studies. This lack of clinical application of research findings is due to several reasons: the lack of “gold standard” for the diagnosis, the complex pathophysiology of sepsis, which involves many processes as inflammation, immunity, coagulation, etc. Thus, we studied the prognostic value of surface molecule expression on lymphocytes and serum levels of the main cytokines, chemokines and adhesion molecules to classify the survival of the patients with septic shock. First, we demonstrated a severe redistribution of T lymphocyte subsets in patients with septic shock. A different kinetic pattern of T cell subset involvement is observed in surviving and nonsurviving patients, with lower numbers of circulating CD3+CD8+CD28+ and CD3+CD8+CD62L+ cells being associated with a better disease outcome (Monserrat et al. 2009b). Second, we have also studied the predictive value for outcome of combining different T-cell, B-cell and NK-cell markers in septic shock patients. We have found a set of five immunophenotypic variables CD3+CD8+CD28+, CD3+CD8+CD45RA+CD45RO-, CD19+CD80+, CD56+CD69+, CD3+CD11a br+CD11b+ cells blood counts that improve the prediction for outcome in septic shock patients to a sensitivity of 94% and a specificity of 100% (Monserrat et al. 2009a).