Therapeutic potential of targeting IL-17 and IL-23 in sepsis

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.