Adsorption of inflammatory cytokines using a heparin-coated extracorporeal circuit

Cardiopulmonary bypass (CPB) surgeries cause an increase in plasma inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) along with whole-body inflammatory responses. The inflammatory responses during a CPB treatment are reduced when using a heparin-coated extracorporeal circuit. Because many cytokines, growth factors, and complements are known to interact with heparin, the reduction of inflammatory responses by a heparin-coated circuit is likely to depend on this heparin-binding nature of the inflammatory cytokines. In this study, the inflammatory cytokines, TNF-alpha and IL-6, in fetal bovine serum (FBS) bound to a heparin-agarose beads (heparin beads)-column and the adsorptions were competitively inhibited on addition of heparin in a concentration-dependent manner. TNF-alpha in FBS required a higher concentration of heparin (50% concentration inhibition [IC50]> 20mug/ml) to inhibit adsorption to the heparin beads-column compared with IL-6, probably because of a stronger interaction between TNF-alpha and heparin-beads. TNF-alpha and IL-6 concentrations in human heparinized blood significantly increased after a CPB treatment. Although the adsorbed amount of IL-6 onto the heparin-coated circuit was low (less than 6% of free circulating IL-6), a significant amount of TNF-alpha adsorbed onto the circuit (23.9-755% of free circulating TNF-alpha). Therefore, the adsorption of inflammatory cytokines, especially TNF-alpha, onto the inner heparin-coated surface of an extracorporeal circuit may partly account for a reduction in inflammatory responses.