Cardiopulmonary bypass decreases cytokine production in lipopolysaccharide-stimulated whole blood cells:: Roles of interleukin-10 and the extracorporeal circuit

Objective: To determine whether cardiopulmonary bypass (CPB) alters the ex vivo cytokine production of whole blood cells stimulated by lipopolysaccharide (LPS) and to assess the roles of interleukin (IL)-10 and an extracorporeal circuit (EGG) in the alteration. Design: Prospective, controlled study. Setting: Biochemistry laboratory and surgical intensive care unit in a university hospital. Patients: Seventeen consecutive adult patients undergoing coronary artery bypass grafting or valve surgery with normothermic CPB and eight healthy volunteers. interventions: Blood samples for cytokine measurement were drawn from patients before and during (at 60, 90, 120, 180 and 360 mins) CPB and were cultured with and without LPS and with and without anti-IL-10 antibodies. Blood was also drawn from healthy subjects and sampled far cytokine analysis before and during circulation in an isolated EGG. Measurements and Main Results: The concentrations of ex vivo tumor necrosis factor (TNF)-alpha, IL-6, IL-8, and IL-10, measured by enzyme-linked immunosorbent assay, were reduced in both experimental settings. In patients on GPB, LPS hyperesponsiveness was detected at 60 mins after the onset of GPB and was maximal at 120 mins (78% to 86% decreases from pre-CPB levels) but was transient, except for TNF-alpha. The plasma concentration of IL-10 peaked at 90 mins after the start of CPB, but the role of IL-10 in LPS hyporesponsiveness appears limited because anti-IL-10 antibodies significantly increased ex vivo production of IL-6 but not TNF-alpha or IL-8. In the isolated ECC study, no IL-10 was detected in plasma, yet the ex vivo production of the cytokines (except IL-8) was decreased (by 66% to 95%). Conclusion: Our results demonstrate the following: a) GPB induces an early and transient LPS hyporesponsiveness of whole blood as measured by cytokine production; b) IL-10 seems only partly involved in this process, and its role is restricted to an in vive situation; and c) contact of blood with an ECC is sufficient to induce LPS hyporesponsiveness.