Abstract
Severe sepsis is a major concern of public health in industrialized countries. It is estimated that in the United States 200,000-400,000 cases occur annually and resulting in an extensive burden for the health care systems. To date, no FDA-approved pharmacologic agents for the treatment or prevention of human sepsis are available. The current modalities of therapy in sepsis include the standard arsenal of supportive interventions in critical care medicine and pharmacotherapy, with use of antibiotics and catecholamines. Despite such efforts, the mortality rates of sepsis have remained around 30-50 %. Extensive scientific studies have utilized animal models of disease and aimed for a better understanding of the pathophysiologic mechanisms during sepsis. Members of the IL-17 family of cytokines, as well as the functionally related IL-23, have been identified as new players in the molecular events during sepsis. Strategies for targeting these mediators with neutralizing antibodies during experimental sepsis in rodents have demonstrated efficacy, resulting in improved survival outcomes. Currently, it is not clear whether such findings can be translated to human sepsis. This review highlights the current knowledge on the biology of IL-17 isoforms and IL-23 as well as potential applications to clinical medicine.
Highlights
Severe sepsis is a major concern of public health in industrialized countries
Cellular Sources of IL-17 s and IL-23 It is widely agreed that macrophages and dendritic cells are the major cell sources contributing to the rapid release of IL-23 during disease
The capability of macrophages to induce IL-17 gene expression may depend on the origin of the macrophages, since IL-17A production after LPS was observed in murine peritoneal elicited macrophages and alveolar macrophages but not in bone marrow derived macrophages after 7 days of maturation in vitro [6]
Summary
Severe sepsis is a major concern of public health in industrialized countries. It is estimated that in the United States 200,000-400,000 cases occur annually and resulting in an extensive burden for the health care systems. IL-17 was first found to be expressed by activated T cells [2]. It should be cautioned that the results of such studies may not apply to all biological functions of IL-17 family members or to all clinical situations in which IL-17 cytokines are expressed. The complement cleavage product, C5a, at higher doses (25–100 nM) interferes with gene expression and release of IL-17 family members following LPSactivation of macrophages.
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