Blood transfusion is associated with well-known risks. We investigated the difference between a restrictive versus a liberal transfusion strategy on the immune response, as expressed by the production of inflammatory mediators, in patients subjected to major abdominal surgery procedures. Fifty-eight patients undergoing major abdominal surgery were randomized preoperatively to either a restrictive transfusion protocol or a liberal transfusion protocol (with transfusion if hemoglobin dropped below 7.7 g dL−1 or 9.9 g dL−1, respectively). In a subgroup of 20 patients randomly selected from the original allocation groups, blood was sampled for measurement of IL-6, IL-10, and TNFα. Postoperative levels of IL-10 were higher in the liberal transfusion group on the first postoperative day (49.82 ± 29.07 vs.
15.83 ± 13.22 pg mL−1, P < 0.05). Peak postoperative IL-10 levels correlated with the units of blood transfused as well as the mean duration of storage and the storage time of the oldest unit transfused (r
2 = 0.38, P = 0.032, r
2 = 0.52, P = 0.007, and r
2 = 0.68, P<0.001, respectively). IL-10 levels were elevated in patients with a more liberal red blood cell transfusion strategy. The strength of the association between anti-inflammatory IL-10 and transfusion variables indicates that IL-10 may be an important factor in transfusion-associated immunomodulation. This trial is registered under ClinicalTrials.gov Identifier: NCT02020525.