1. Recent studies have suggested that interleukin-6 is a major mediator of the acute-phase protein response in man. The aim of the present study was to investigate the relationships between the response of serum interleukin-6 to surgery, the type of surgical procedure performed and the response of serum C-reactive protein. 2. Timed venous blood samples were taken from 26 patients in five broad surgical categories (minor surgery, cholecystectomy, hip replacement, colorectal surgery and major vascular surgery). C-reactive protein and interleukin-6 were measured in each sample. 3. Serum interleukin-6 rose within 2-4 h of incision in all patients and the magnitude of the response differed among the various surgical groups. The response of interleukin-6 correlated (r = 0.80, P less than 0.001) with the duration of surgery. In contrast, serum C-reactive protein was not detectable after minor surgery (less than 10 mg/l) and the response of C-reactive protein did not differ among the more major surgical groups. The response of interleukin-6 showed a weak, but significant, correlation with the response of C-reactive protein (r = 0.67, P less than 0.001). 4. We conclude that serum interleukin-6 is a sensitive, early marker of tissue damage. In general, the greater the surgical trauma, the greater the response of serum interleukin-6 and the greater the peak serum concentration of interleukin-6. Our results are consistent with a role for interleukin-6 in the induction of C-reactive protein synthesis.

Metabolic and inflammatory responses and changes in fatigue were studied in groups of patients undergoing either laparoscopic (n = 14) or open (n = 10) elective cholecystectomy. The mean(s.e.m.) cortisol concentration was significantly (P < 0.001) increased from 342(80) and 424(91) nmol l-1 before operation to 895(46) and 966(53) nmol l-1 after surgery in patients undergoing laparoscopic and open cholecystectomy respectively. There was no difference in cortisol response between the groups. Glucose concentration was increased (P < 0.02) at the end of surgery from mean(s.e.m.) preoperative levels of 5.54(0.15) and 6.16(0.15) mmol l-1 to postoperative values of 7.46(0.29) and 8.46(0.86) mmol l-1 for the laparoscopic and open procedures respectively. The mean glucose concentration during the initial 12 h after surgery was significantly greater (P < 0.02) following open than laparoscopic cholecystectomy. The mean(s.e.m.) albumin concentration fell significantly (P < 0.01) during surgery by an equivalent extent from 38.9(0.77) and 38.5(1.10)g l-1 to 35.2(0.79) and 34.6(0.97) g l-1. The mean (95 per cent confidence interval) interleukin (IL)6 concentration peaked 4 h after surgery at 57.2 (44.6-73.4) pg ml-1 following laparoscopic and 99.3 (72.8-135.4) pg ml-1 after open cholecystectomy. Mean (95 per cent confidence interval) C-reactive protein (CRP) levels at 24 h were 17.0 (12.7-21.2) and 49.0 (25.3-93.6) mg l-1 and at 48 h 28.0 (21.4-35.4) and 70.0 (36.4-133.6) mg l-1 following laparoscopic and open operations. The differences in IL-6 and CRP level between the groups were significant (P < 0.01). Mean(s.e.m.) fatigue scores were significantly (P < 0.05) increased from preoperative values of 2.4(0.24) and 2.6(0.44) to 5.5(0.56) and 6.8(0.51) at 24 h after laparoscopic and open operations. At 48 h the mean(s.e.m.) fatigue score (5.6(0.57)) remained significantly (P < 0.05) raised only after open cholecystectomy. Hand grip strength was significantly (P < 0.05) reduced only after the open procedure, to a mean(s.e.m.) of 88(6) per cent of the preoperative value. These results demonstrate that aspects of the metabolic and acute-phase responses are attenuated following laparoscopic cholecystectomy, consistent with a reduction in tissue trauma.

We studied the relationship between the neuroendocrine and inflammatory responses to hip arthroplasty and functional recovery in 102 patients undergoing elective arthroplasty for osteoarthritis. Blood samples were collected for up to 7 days after surgery and analysed for concentrations of norepinephrine, epinephrine, cortisol, interleukin-6 and C-reactive protein. The primary outcome measures were milestones in hospital, times to walk 10 and 25 m, pain on discharge from hospital, and function 1 and 6 months after surgery. Walking distances in hospital were significantly delayed in patients with greater interleukin 6 and C-reactive protein concentrations, but few neuroendocrine measures had significant correlations with functional recovery in hospital. Multivariate analysis showed that the interleukin 6 concentration on day 1 was the unique predictor of time to walk 10 and 25 m, and that the day 2 concentration of C-reactive protein was the unique predictor of pain on discharge from hospital. No significant correlations were found between the inflammatory and neuroendocrine variables and recovery at 1 and 6 months. We conclude that the inflammatory response affects immediate functional recovery after hip arthroplasty.

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