Decreased immunoreactivity and binding activity of corticosteroid-binding globulin in serum in septic shock

To investigate the mechanism(s) responsible for the depletion of corticosteroid-binding globulin (CBG) activity in serum in septic shock, we developed a radioimmunoassay (RIA) for human CBG, using a monospecific antiserum to human CBG raised in rabbits. CBG was purified from pooled human serum by precipitation with ammonium sulfate and successive affinity chromatography treatments on corticosterone-Sepharose and concanavalin A-Sepharose. Final purification was achieved by HPLC on a diethylaminoethyl-PW (polymer matrix) ion-exchange column. Typical standard curves established for the CBG immunoassay showed parallelism for pure CBG and serial dilutions of sera from patients with septic or nonseptic shock and from healthy controls. Measurements of CBG by RIA showed a significantly (P less than 0.001) lower CBG concentration in patients with septic shock (22.9 +/- 5.9 mg/L, mean +/- SD; n = 23) than in controls (39.9 +/- 6.5 mg/L, n = 21) or in patients with nonseptic shock (33.3 +/- 6.5 mg/L, n = 12). The correlation between the concentrations determined by RIA and the CBG binding capacity was significant (r = 0.619, P less than 0.001, n = 33). The electrophoretic mobility of CBG was similar in sera from septic shock patients and normal subjects (Rf = 0.52-0.56). This suggests that the depletion of the corticosteroid-binding activity in serum during septic shock is associated with a decreased amount of CBG.