IL-6 as a Marker of Excessive TNF-α Activity in Sepsis

Abstract

The proinflammatory response triggered by infection and injury is initially protective and mediated by a number of host factors including tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and IL-8. In excess, these factors may cause severe tissue damage and life-threatening physiologic perturbations. If patients with a hyperinflammatory response can be identified early, they may benefit from treatment aimed at attenuating this response. In experimental models of sepsis, proinflammatory cytokines appear in the circulation in a relatively ordered manner but clinical sepsis is not as predictable. Compromised response mechanisms, interfering physiologic disturbances and therapeutic agents, and a variable temporal relationship to the onset of infection probably all contribute to the wide variability in both frequency and magnitude of their appearance seen in different studies. Although TNF-α is a proximal mediator of sepsis, circulating TNF-α concentrations at the time of diagnosis do not consistently correlate with disease severity. IL-6 is induced by TNF, appears in the circulation after the initial TNF response, often remains elevated, and is more consistently measurable. These properties may make it a good surrogate measure of localized TNF-α activity. In numerous studies, IL-6 was consistently shown to be elevated in septic patients, and serum concentrations correlated well with measures of disease severity and mortality. Assessing circulating IL-6 at the time of sepsis diagnosis may enable treatment decisions that are more directed to the individual patient's inflammatory response.