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 (ECC) 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 for cytokine analysis before and during circulation in an isolated ECC. 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 CPB, LPS hyporesponsiveness was detected at 60 mins after the onset of CPB 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) CPB 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 vivo situation; and c) contact of blood with an ECC is sufficient to induce LPS hyporesponsiveness.

Sequential study of serum glycoprotein fucosylation in acute hepatitis.

BACKGROUND: alpha-Fetoprotein is a useful diagnostic marker in hepatocellular carcinoma, during which its serum level increases and its glycan structure is hyperfucosylated. Normally-expressed glycoproteins (alpha 1-antitrypsin and transferrin) are also hyperfucosylated in hepatocellular carcinoma. alpha-fetoprotein serum levels are also increased in conditions associated with hepatic regeneration, such as acute hepatitis. We conducted a longitudinal study of the alpha 1-6 fucosylation pattern of serum alpha-fetoprotein in ten patients with acute hepatitis and compared it to that of transferrin and alpha 1-antitrypsin. METHODS: Protein levels were measured by using immunochemical assays. Crossed affinoimmunoelectrophoresis in the presence of Lens culinaris agglutinin was performed for each protein, and the fucosylation index, corresponding to the agglutinin reactive fraction, was determined. The results were compared to those in 25 healthy donors and five newborns. RESULTS: alpha-Fetoprotein was hyperfucosylated and remained stable throughout the course of the disease. In contrast, serum transferrin and alpha 1-antitrypsin gradually became hyperfucosylated during the course of acute hepatitis. The transferrin and alpha 1-antitrypsin fucosylation indexes correlated with each other, but not with the alpha-fetoprotein fucosylation index. No correlation was found between alpha-fetoprotein, alpha 1-antitrypsin and transferrin fucosylation indexes and the corresponding glycoprotein serum levels. CONCLUSIONS: Hyperfucosylation of alpha-fetoprotein is not specific to hepatocellular carcinoma. Increased alpha 1-6 fucosylation should not be considered solely as a tumour marker, but might also reflect cell proliferation. The study of alpha 1-6 hyperfucosylation process of normally-expressed glycoproteins awaits further investigation, to test its usefulness as a new marker of liver regeneration during the follow-up of acute hepatitis.