Journal
EXPERT OPINION ON EMERGING DRUGS
Volume 17, Issue 3, Pages 379-391Publisher
TAYLOR & FRANCIS LTD
DOI: 10.1517/14728214.2012.697151
Keywords
cytokines; hydrocortisone; immunoglobulins; macrolides; polymyxin B; sepsis
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Funding
- ABBOTT Hellas SA
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Introduction: Despite improvement in medical care, severe sepsis and septic shock remain an unmet medical need. Their incidence is steadily increasing and the worldwide mortality ranges between 30% and 50%. This generates the need for agents that modulate the immune function of the host. Areas covered: Available agents can be divided into three categories according to their mechanism of action: i) agents that block bacterial products and inflammatory mediators. Hemoperfusion with polymyxin B embedded fiber device that blocks bacterial lipopolysaccharides (LPS) has given promising clinical results. Blockade of TNF-alpha with afelimomab and CytoFab appears promising; ii) modulators of immune function. Hydrocortisone stress replacement, intravenous infusion of clarithromycin and immunonutrition with omega-3 (omega-3) polyunsaturated fatty acids (PUFAs) have all yielded positive clinical results. Recombinant thrombomodulin for patients with disseminated intravascular coagulation appears a promising alternative; and iii) immunostimulation. Meta-analysis of conducted trials disclosed the decrease of mortality in septic shock after administration of immunoglobulin preparations enriched with IgM. Expert opinion: The underlying pathophysiologic mechanisms in septic patients are highly individualized. As such, specific tools should be developed in the near future to define these differences and tailor therapeutic strategies accordingly.
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