Impact of surgery on local and systemic responses of cytokines and adhesion molecules

Operation may result in various kinds of biological responses in patients who undergo surgery. Recent studies revealed cytokine network is greatly involved in the biological response to surgical stress, as sepsis. Extended surgical injuries may result in a deregulated hyperinflammatory response. However, cytokine and adhesion molecule dynamics of the local area and circulatory blood in perioperative period have not been well clarified.

18 patients with colorectal cancer undergoing operation were recruited into the study. The patients were without major systemic disease and without postoperative complications. Serum samples were taken before operation (Preop) and on post-operation day 1 (POD1), day 3 (POD3), and day 7 (POD7). Samples from the drain tube (local) were taken on POD 1, 3, and 7. Interleukin-6 (IL-6) and adhesion molecules, including ICAM-1, P-selectin, E-selectin, and L-selectin, in serum and drain fluid were measured using ELISA.

Serum IL-6 was lowest at Preop, and elevated and peaked on POD1. IL-6 levels in serum were significantly lower than those in drain fluid on POD1, 3, and 7. Circulatory IL-6 after surgery is speculated to come mainly from the surgical traumatic area. Serum P-selectin elevated after the operation and peaked on POD1. P-selectin in drain fluid also peaked on POD1. P-selectin in serum was significantly higher than that in the drain fluid on POD1, 3, and 7. By contrast to IL-6, circulatory P-selectin may come from sources other than the local area. Serum ICAM-1 diminished from Preop to POD1, and to POD3. ICAM-1 in drain fluid elevated from POD1 to POD3, and also from POD3 to POD7. ICAM-1 in drain fluid was significantly lower than that in serum on POD1 and 3. The operation resulted in a significant decrease in systemic soluble ICAM-1 levels, which may associate the patients wtih post-operative organ failure. Serum and drain fluid E-selectin and L-selectin dynamics exhibited a similar pattern to that of ICAM-1.

For the first time, we demonstrate that surgery induced distinguished dynamic differences between local and systemic cytokine and adhesion molecule response. Circulating IL-6 and P-selectin incresaed after surgery and peaked on POD1. By contrast, surgery diminished the circulating ICAM-1 and E-selectin. Modulation of cytokine and adhesion molecule responses in the perioperative period, for example with nutritional or anticytokine therapy, may have potential clinical importance.