Sepsis and cytokines: current status

Sepsis is a constellation of clinical signs and symptoms resulting from excessive systemic host inflammatory response to infection. This inflammatory response is largely mediated by cytokines, which are released into the systemic circulation. Plasma concentrations of specific cytokines, TNF alpha, IL-1 beta, IL-6 and IL-8 are frequently elevated in human sepsis and cytokine concentrations correlate with severity and outcome of sepsis. In addition to pro-inflammatory cytokines, soluble cytokine receptors, cytokine receptor antagonists and counter-inflammatory cytokines are also produced in large quantities in patients with sepsis; however, the specific role of these molecules in sepsis remains undefined. A complex interaction of cytokines and cytokine-neutralizing molecules probably determines the clinical presentation and course of sepsis. Intervening in this sequence of events to modify the host inflammatory responses may prove to be a beneficial treatment strategy for sepsis, but currently tested anticytokine therapies have been largely unsuccessful.