The restraint stress-induced elevation in plasma interleukin-6 negatively regulates the plasma TNF-alpha level

Although a considerable amount of evidence has shown that physical and psychological stress elevates the plasma interleukin 6 (IL-6) levels, the physiological significance of such an elevation remains to be elucidated. In this study, in order to determine whether the restraint stress-induced elevation of plasma IL-6 contributes to the activation of the hypothalamic-pituitary-adrenal axis, and whether or not such elevation can affect the inflammatory processes, the plasma levels of ACTH, corticosterone, interleukin-1 (IL-1), and tumor necrosis factor-alpha (TNF-alpha) in mice pretreated with anti-IL-6 antibody (MP5-20F3 monoclonal antibody) were compared with those in mice pretreated with rat IgG (control antibody) both during and after stress. Both the anti-IL-6-antibody- and control-antibody-pretreated mice showed the same extent of plasma ACTH and corticosterone increases during stress, and no significant difference was found between the two groups of animals. On the other hand, the level of plasma TNF-alpha in the anti-IL-6-treated animals was also significantly higher than that in the control animals both immediately after cessation of stress and 60 min after the cessation of the 120-min period of restraint. Plasma IL-1 activity, however, did not reach a detectable level in either group of animals at any time point examined. These results thus indicate that the restraint-stress-induced elevation of plasma IL-6 negatively regulates the plasma TNF-alpha levels and may thus contribute to the maintenance of homeostasis.