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Abstract Intensive care unit (ICU) mortality rate for severe sepsis and septic shock is ranging from 20% for sepsis to 40% for severe sepsis, and to >60% for septic shock [11]. Sepsis occurs as a result of the complex interactions of the offending pathogens with the innate and adaptive immune systems. Microbial pathogens bear well-conserved structures, known as pathogen associated molecular structures (PAMPs), which interact with receptors in cells of the innate immune system including the cell-surface toll-like receptors and several types of cytoplasmic receptors. Receptor binding results in activation of intracellular signaling pathways that lead to a variety of responses, including increased transcription of inflammatory cytokines, stimulation of humoral and cell-mediated immune responses, and activation of vascular endothelial cells [14]. The treatment of severe sepsis and septic shock consists of control of source of infection, early antimicrobial therapy, and supportive and adjunctive therapies. Further reduction in mortality may be achievable through early-goal directed management of hypotension and perfusion abnormalities with fluid resuscitation and vasoactive agents [17]. The prominent role of inflammatory molecules and pathways suggests a possible therapeutic role in the management of severe sepsis and septic shock. Immunomodulation is a therapeutic intervention intended to either stimulate or suppress a particular immune response. Numerous trials of immunomodulation targeted at inhibiting various essential inflammatory mediators and receptors involved in sepsis. This includes the use of activated protein C, corticosteroids, heparin, hemofiltration, statins, glutamine, insulin, inhibition of apoptosis and nitric oxide. Hypertonic saline solution, intravenous immunoglobulins, anti tumor Necrosis Factor- , macrolides, neuroimmunomodulation, mesenchymal stem cells and colony stimulating factors have been also tried. Corticosteroids and activated drotrecogin alfa are to date the only drugs that have demonstrated mortality benefits in large randomized controlled trials [153]. Before using immunomodulatory therapies one should be alert about their mechanism of action, also when to start these therapies and how to choose patients who may benefit of these drugs to avoid their complications [401]. |