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 (LL)-1 beta, and ex-vivo production of IL-1 beta and tumour nec rosis 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 valu es (mean +640% +/- 400, P < 0.05). In a more detailed study in six patients, the ex-vivo production of IL-1 be ta and TNF-alpha started to decrease at induction of general anaesthesia an d 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 antidiu retic hormone (ADH) and adrenocorticotropic hormone (ACTH) increased during surgery, but cortisol remained unchanged. We demonstrate a depression of circulating pro-inflammatory IL-1 beta and a n increase of circulating anti-inflammatory IL-1ra during surgical stress. The ex-vivo production of IL-1 beta and TNF-alpha was suppressed, indicatin g a downregulation of the production of these cytokines. This parallelled t he hormonal reaction with high ADH and ACTH, but not of cortisol, suggestin g that glucocorticoid is not the key-factor in downregulation of production and release of pro-inflammatory cytokines. (C) 1999 Academic Press.