Possible Role of Cytokines in the Stress Response of the Hypothalamo-Pituitary-Adrenal Axis During Upper Abdominal Surgery

It is well known that surgical invasion activates the hypothalamo-pituitary-adrenal (H-P-A) axis and induces marked elevation in plasma adrenocorticotropic hormone (ACTH) and Cortisol levels during and after surgery. The stress response of plasma ACTH and Cortisol levels cannot be totally suppressed by epidural [1] or subarachnoid anesthesia [2], especially in upper abdominal surgery [3], which suggests the involvement of some factor(s) other than afferent neural output arising from the injury site [4]. Some cytokines have recently been suspected to play important roles in the activation of the H-P-A axis at the times of infectious challenge and other stressful conditions [5–7]. To assess the possible involvement and role of cytokines in the stress response of the H-P-A axis during surgical procedures, we observed changes in the levels of plasma ACTH, Cortisol, endotoxin, tumor necrosis factor-alpha (TNF-α), interleukin-1 (IL-1), and interleukin-6 (IL-6) in patients undergoing upper abdominal surgery. We then investigated the ACTH-releasing activities of these cytokines using an in vivo experimental system.