Objective: Severe inflammation and sepsis remain a serious clinical challenge worldwide. Despite modern supportive medicine and an improved understanding of the underlying pathophysiology, mortality rates remain high in patients suffering from this severe inflammatory process. The often excess production of pro- and anti-inflammatory cytokines frequently found in the circulation of septic patients has stimulated the search for reliable inflammatory mediators that can be used for the diagnosis and prediction of clinical outcome. Interleukin (IL)-18, formerly termed interferon-gamma inducing factor, is a pro-inflammatory and Th1 cytokine suggested to play a significant role in the pathogenesis of this disease. This review focuses on our current understanding of the pro-inflammatory cytokine, IL-18, and its potentially unique role in sepsis.
Methods: Bibliographic search of the most recent literature (1995-2005) relating to IL-18 and its role in inflammatory diseases, with emphasis on its pathophysiological importance in sepsis. In addition, a summary of the author's own experimental data from this particular field of research set in the context of current knowledge regarding IL-18.
Results and conclusions: Several studies have shown elevated plasma IL-18 concentrations to be associated with poor clinical outcome in severe inflammatory and septic conditions. Moreover, a significant increase in IL-18 concentrations has been shown to discriminate between Gram-positive and Gram-negative related sepsis, and, thus, may potentially augment existing diagnostic tools. Biological neutralization of IL-18 via caspase-1 intervention or through the administration of IL-18-binding protein has been promulgated as a promising therapeutic approach, but additional studies are required to evaluate its full potential in acute inflammatory diseases.