Postoperative serum attenuates LPS-induced release of TNF-α in orthopaedic surgery

Studies with ex vivo stimulation of whole blood samples from injured patients have revealed a diminished production capacity for a broad range of secretory products, including inflammatory cytokines. Recent interest has focused on the release of mediators in serum that depress the cell‐mediated immune response following trauma. The involvement of the lipid mediator prostaglandin E2 (PGE2) has been assumed because it is a potent endogenous immunosuppressor. In the present study, we tested the hypothesis that inhibitory substances circulating in the patient's serum after a major musculoskeletal trauma might impair leukocyte function by evaluating the effect of such serum on cytokine release in a whole blood model. Six females and three males undergoing elective total hip replacement were included in the study. Ex vivo LPS‐induced TNF‐α and IL‐10 were measured in whole blood sampled preoperatively and added serum taken before, at the end of operation, and at postoperative days 1 and 6 with saline as negative control. LPS induced significant releases of TNF‐α and IL‐10 in whole blood. Addition of preoperative, postoperative, and day‐1 postoperative serum did not alter the LPS‐induced release of TNF‐α as compared to saline. In the presence of serum from postoperative day 6, however, the expression of TNF‐α was significantly reduced as compared to saline and preoperative serum (p = 0.021 and 0.008, respectively). Neither of the serum samples altered the release of IL‐10. PGE2 was significantly (p = 0.008) increased in serum at postoperative day 6 as compared to preoperative levels. In conclusion, these data show that at day 6 after major orthopaedic surgery, the patient serum contained activity that inhibited ex vivo LPS‐induced TNF‐α release. The potent TNF‐α inhibitory activity found at day 6 after injury correlated with increased levels of PGE2 and indicates cell‐mediated hyporesponsiveness to a second stimulus. © 2007 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 25:1395–1400, 2007