Immunomodulation in sepsis: the role of hemofiltration

Inflammation is a normal and biologically important process essential for host defense and repair of tissue injury. However, given the cyto-destructive capacity of inflammation, it is tightly controlled even in severe sepsis. There are both pro- and anti-inflammatory components of the inflammatory response, which are initiated simultaneously and co-exist in a single organism. Significant morbidity and mortality results when the inflammatory response becomes unstable and its components uncoupled. Restoring immune stability likely requires reestablishing a balance between pro- and anti-inflammatory processes as well as restoring the normal feedback mechanisms necessary for systemic control. Selective manipulation of inflammation by augmenting or blocking specific components continues to fail as a therapeutic approach to human sepsis, perhaps because such targeted manipulation of the immune response is unable to restore balance and immune stability. It has been recently shown that continuous veno-venous hemofiltration (CVVH) can nonselectively affect the plasma concentrations of immune mediators in patients with sepsis and multiple organ dysfunction syndrome (MODS). Hemofiltration offers tremendous potential advantages over other forms of immunomodulation because it is both non-specific and self-regulating. CVVH can remove both soluble pro- and anti-inflammatory substances and does so in direct relationship to the circulating mediator concentrations. The ultimate value of this technique will depend on whether immunomodulation is an appropriate goal for patients with sepsis. The avoidance of unintended immunomodulation is also an important issue, and evidence already suggests that this should be a priority.