It has recently been reported that both physical and psychological stress elevate plasma interleukin (IL)-6 levels independently of endotoxemia, tissue damage, or inflammation. However, the mechanism of plasma IL-6 elevation in these models is poorly understood. In the present study, plasma IL-6 levels were measured using the IL-6-dependent murine hybridoma subclone B9 cell line, which is commonly used by other investigators. We first demonstrated that an immobilization (IM) stress, a typical physicopsychological stress, increased plasma IL-6 levels. Then the contribution of the hypothalamic-pituitary-adrenal (HPA) axis and the central and peripheral catecholaminergic systems in IM-induced plasma IL-6 elevation were examined because these mechanisms play important roles in host defense against stress. Blood samples were collected through an indwelling jugular venous catheter before, during, and after IM; the number of samples taken serially from each animal was 12-13. Blood cells were resuspended in a saline solution and injected into the animals through the same catheter after each blood collection in order to prevent loss of blood volume. After initiation of restraint, plasma IL-6 levels significantly increased at 60 min and peaked at 90 min in the animals immobilized for either 30 or 120 min. The peak levels of IM-induced plasma IL-6 in the animals immobilized for 120 min (1,905 +/- 414 U/ml) were significantly higher than those in the animals subjected to 30 min IM (837 +/- 95 U/ml; p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)