An in vitro system composed of a plasma separation membrane coupled with natural (charcoal) or synthetic (Amberlite, Amberchrome) types of sorbents was evaluated for the simultaneous removal of proinflammatory cytokines (TNF-alpha, IL-1 beta and IL-8) and cytokine antagonists [interleukin (IL)-1 receptor antagonist (IL-1Ra), soluble tumor necrosis factor-alpha (TNF-alpha) receptor I and II (sTNFR I and II)] in whole blood spiked with bacterial lipopolysaccharide (LPS). These studies showed that plasma filtration rather than ultrafiltration significantly increased the clearance of all cytokines, particularly TNF-alpha, and the synthetic (Amberlite-type of resin) but not natural (uncoated charcoal) membrane could extensively absorb almost 100% of plasma filtered IL-Ra, IL-1 beta and IL-8, but only 40% of TNF-alpha. Other synthetic (Amberchrome) membranes could also effectively (80%) remove TNF-alpha. In the complex scenario of sepsis, the simultaneous removal of excess proinflammatory and/or immunomodulatory mediators may play a role in reducing the hemodynamic alterations, thus resulting in enhanced patient survival. Whether this occurs in the human setting awaits the results of an ongoing clinical investigation.