Pain and Analgesic Doses Versus Free Interleukin 18 (IL-18F) Blood Levels Following Surgery: A Prospective Randomized Study of Patients With Minilaparotomy Cholecystectomy Versus Laparoscopic Cholecystectomy

Background/Aim: Cytokines (CYT) are regulators of the acute phase immune response (APR) to inflammation and trauma. The purpose of this work was to assess blood level correlations of various CYTs; interleukin-18 (IL-18), IL-18 binding protein (IL-18BP), free interleukin 18 (IL-18F) versus numerical rating pain scale (NRS) and number of analgesic doses (NAD) following surgery in patients undergoing laparoscopic cholecystectomy (LC) or minilaparotomy cholecystectomy (MC). Patients and Methods: Blood levels of IL-18, IL-18BP, IL-18F and five CYTs were determined and the NRS pain surveys were performed preoperatively (PRE) and postoperatively (POP). Results: The IL-18F blood levels correlated to IL-18 (r=0.92, p<0.001), IL-18BP (r=−0.260, p<0.001), Caspase-1 (r=0.64, p<0.001), catalase (r=0.13, p<0.04), and nitrotyrosine (r=−0.16, p=0.01) blood levels. The IL-18F blood levels increased at POP and the increase between PRE and POP2 blood levels (632 versus 739) was significant (p<0.01). Moreover, the IL-18F and IL-18BP levels correlated significantly to NRS pain scales (r=−0.16, p=0.02 and r=0.17, p=0.02, respectively) and to the NAD levels (r=−0.20, p=0.016 and r=−0.16, p=0.05, respectively) in patients with cholecystectomy. Conclusion: This is the first report to demonstrate that postoperative IL-18F levels are significantly associated with NRS pain scores and the number of analgesic doses in patients undergoing cholecystectomy. These findings suggest that IL-18F and IL-18BP may contribute to the acute-phase immune response to surgical trauma and its relationship with postoperative pain and analgesic requirements.