Depression of plasma levels of cytokines and ex-vivo cytokine production in relation to the activity of the pituitary-adrenal axis, in patients undergoing major vascular surgery.

The relation between the immune and neuroendocrine response during surgery was studied. In 18 patients undergoing major vascular surgery, circulating interleukin (IL)-1beta and ex-vivo production of IL-1beta and tumour necrosis factor (TNF)-alpha were lower on day 1 after surgery compared to pre-operation values (-14+/-5%, P<0.05; -62+/-9%, P<0.05; and -31+/-54%, P<0.005, respectively). Circulating IL-1 receptor antagonist (IL-1ra) was higher on the 5th day post-operatively compared to pre-operation values (mean +640%+/-400, P<0.05). In a more detailed study in six patients, the ex-vivo production of IL-1beta and TNF-alpha started to decrease at induction of general anaesthesia and dropped to under 10% of initial values at the end of surgery. Circulating IL-1ra and ex-vivo production of IL-1ra started to increase at the end of surgery and remained elevated up to 6 days post-operatively. Plasma antidiuretic hormone (ADH) and adrenocorticotropic hormone (ACTH) increased during surgery, but cortisol remained unchanged. We demonstrate a depression of circulating pro-inflammatory IL-1beta and an increase of circulating anti-inflammatory IL-1ra during surgical stress. The ex-vivo production of IL-1beta and TNF-alpha was suppressed, indicating a downregulation of the production of these cytokines. This parallelled the hormonal reaction with high ADH and ACTH, but not of cortisol, suggesting that glucocorticoid is not the key-factor in downregulation of production and release of pro-inflammatory cytokines.