Immunity, inflammation and sepsis: new insights and persistent questions.

Sepsis is now understood to affect a variety of changes in the host, chief among them being alterations in immune system function. Proper immune function involves a competent proinflammatory response to stimuli as well as a regulated counteracting force to restore homeostasis and prevent systemic inflammation and organ dysfunction. Broad-spectrum suppression of the inflammatory response has not been shown to be beneficial for patients suffering from septic disease. In fact, sepsis-related immune suppression has become increasingly recognized as an important contributor to late morbidity and mortality in the critically ill. Giamarellos-Bourboulis and colleagues detail the impaired ability of septic patients to produce proinflammatory cytokines upon ex vivo stimulation, and introduce altered caspase-1 activity as potentially contributory to this process. Proper understanding of the cellular and molecular events resulting in immune suppression following sepsis is important in the identification of new strategies for treatment and the ideal timing of therapy.