Depletion of circulating insulin-like growth factor binding protein 3 after open surgery is associated with high interleukin-6 levels

PURPOSE: We have previously shown that plasma from open, but not laparoscopic-assisted, surgery patients has increased mitogenic activity for colon cancer cells. Decreased insulin-like growth factor binding protein 3 levels, most likely the result of an open surgery-induced proteolytic activity, may account for this finding. Plasma proteases are activated by interleukin-6. This study was designed to investigate plasma insulin-like growth factor binding protein 3 and interleukin-6 levels after major open or laparoscopic-assisted surgery. METHODS: EDTA plasma was obtained from 24 patients undergoing resection for colonic adenocarcinoma. Insulin-like growth factor binding protein 3 was detected by Western blot analysis and enzyme-linked immunosorbent assay. Interleukin-6 levels were determined by enzyme-linked immunosorbent assay. The effect of insulin-like growth factor binding protein 3 on tumor growth was tested using HCT 116 cells. RESULTS: In patients undergoing open surgery, enzyme-linked immunosorbent assay revealed a significant decrease in total insulin-like growth factor binding protein 3 levels on postoperative Day 1 (915.6 ± 378.5 ng/ml) compared with preoperative levels (1,267.5 ± 407.9 ng/ml; P < 0.001). Western blots revealed a decrease in the levels of intact insulin-like growth factor binding protein 3. In patients undergoing laparoscopic-assisted surgery, levels of total and intact insulin-like growth factor binding protein 3 before surgery (1,088.9 ± 232.5 ng/ml) and on postoperative Day 1 (1,202.3 ± 285.6 ng/ml) were comparable with no significant changes in Western blot analysis. Interleukin-6 levels were undetectable preoperatively. On postoperative Day 1, interleukin-6 concentration was higher in open surgery group (434.8 ± 506.6 pg/ml) compared with laparoscopic-assisted surgery group (100.9 ± 60.2 pg/ml; P < 0.0001), and correlated significantly with a decrease in plasma insulin-like growth factor binding protein 3 after open surgery (r = 0.81; P < 0.0001). CONCLUSIONS: A significant decrease in both total and free insulin-like growth factor binding protein 3 occurs after open but not laparoscopic colectomy. There is an associated increase in the levels of interleukin-6. It remains to be proven that the interleukin-6 elevations are responsible for the low insulin-like growth factor binding protein 3 level seen after open surgery.