Can the interleukin-1 receptor antagonist (IL-1ra) be a marker of anti-inflammatory response to enteral immunonutrition in malnourished patients after pancreaticoduodenectomy?

OBJECTIVE: To investigate whether early enteral immunonutrition in comparison with standard enteral feeding affects the systemic production of pro- and anti-inflammatory cytokines in malnourished patients after pancreaticoduodenectomy with an uneventful postoperative course.

DESIGN: Prospective, randomized study.

PARTICIPANTS: Forty-one patients who had undergone pancreaticoduodenectomy.

INTERVENTIONS: Patients received early enteral standard nutrition (No. 22) or enteral immunonutrition (No. 19).

MAIN OUTCOME MEASURES: Cytokines and cytokine inhibitors (IL-1 beta, TNF-alpha, IL-6, IL-8, IL-10, IL-1ra, and sTNFRI) were determined before and on days 1, 3, 7, 10 and 14 after surgery using the ELISA test.

RESULTS: Serum concentrations of IL-1ra in the early post-operative period were significantly higher in patients treated with enteral immunonutrition than in those treated with the standard diet (day 7: P<0.001; day 10: P=0.002; day 14: P=0.005). Similar results were observed for IL-6 (day 10: P=0.017; day 14: P=0.001), IL-8 (day 1: P=0.011; days 3, 7, 10, and 14: P<0.001) and IL-10 (days 3 and 10: P<0.001) whereas the post-operative levels of IL-1 beta (day 7: P<0.001; day 14: P=0.022) and TNF-alpha (day 3: P=0.006; day 7: P<0.001) were significantly higher in patients with standard enteral nutrition.

CONCLUSION: Early enteral immunonutrition as compared to standard nutrition has an immunomodulative effect on the changes in the immune response after extensive surgical trauma resulting in the selective stimulation of cytokines and cytokine inhibitors. The interleukin-1 receptor antagonist is the earliest sensitive marker of anti-inflammatory response to enteral immunonutrition in malnourished patients after pancreaticoduodenectomy.