الفهرس 
IntroductionOnly 14 pages are availabe for public view
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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].