[Interleukin-1 beta and interleukin-6-plasma concentrations in laparotomies. Interaction with neuroendocrine...

Elevated body temperature, increased plasma cortisol concentrations, and loss of the circadian secretory pattern are typical changes observed after trauma and surgery. We investigated the hypothesis that the interleukins IL-1 beta and IL-6 are involved in these phenomena, since both are endogenous pyrogens and can induce ACTH and cortisol secretion. METHODS. Eight healthy women undergoing hysterectomy for non-malignant diseases participated in the study after having given written consent. The study had the approval of our institution's ethics committee. Anaesthesia was induced with fentanyl 0.1 mg and methohexitone 1.5 mg/kg and maintained with isoflurane in 60% N2O and 40% O2. Blood samples were drawn before induction, before incision, during surgery, at the end of surgery, and 30, 60, 120, 240 and 360 min after surgery. Cortisol, prolactin, IL-1 beta, and IL-6 concentrations were determined with commercially available ELISAs. Statistical analysis was performed with non-parametric methods. RESULTS. IL-6 increased significantly from 15 (4.3-23) to 68 (18-107) pg/ml (medians and range) at the end of surgery and peaked at 128 (52-214) pg/ml 60 min postoperatively (p < 0.01, Table 2). Baseline IL-1 beta concentrations were 20 (1-35) pg/ml with a significant increase in median postoperative concentrations in the postoperative period (p < 0.001). Prolactin increased from 22 (13-43) to 210 (115-291) ng/ml immediately after induction of anaesthesia (p < 0.001) and remained elevated until 240 min after surgery. Cortisol increased from 99 (26-167) to 384 (241-553) ng/ml during surgery and reached a maximum of 475 (246-597) ng/ml 30 min postoperatively (Table 3). Rectal and mean body temperatures increased significantly in the postoperative period (Table 1). There was a significant correlation between IL-6 and cortisol concentrations (r = 0.468; p < 0.001), but none was found between IL-6 and temperature or between IL-1 beta and cortisol or temperature. CONCLUSIONS. Surgical trauma markedly stimulates the secretion of IL-6, and to a lesser extent that of IL-1 beta. The data do not yield any evidence indicating an effect of IL-1 beta or IL-6 on body temperature. Postoperative prolactin concentrations might be influenced by IL-6. The positive correlation between plasma concentrations of IL-6 and cortisol may be coincidental, but could reflect a causal relationship, particularly in the postoperative period during which time the circadian pattern of cortisol secretion is disturbed.