Immune Modulation after Total Hip Surgery

Abstract

Background: Major trauma affects the immune system, and immunosuppression may render the patients susceptible to septic complications. The purpose of this study was to investigate lipopolysaccharide (LPS)-induced releases of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in whole blood in patients undergoing total hip replacement. Methods: Seven patients (6 females) who underwent elective total hip replacement were included. Ex vivo LPS-induced releases of TNF-α and IL-6 were measured in a whole blood assay at days 1, 6, 9 and 12 postoperatively, using low- and high-dose LPS incubation. At the same time, white blood cell counts were analyzed. Results: The amount of TNF-α release was significantly reduced at days 6 and 12. Compared to monocyte counts, TNF-α release was significantly decreased also at day 9 in low- and high-dose LPS stimulation. IL-6 in plasma was significantly increased at day 1 and normalized thereafter. There were no differences in LPS-induced IL-6 levels compared to the levels before surgery. Conclusion: This in vivo/ex vivo study shows a reduced capacity of whole blood to release LPS-induced TNF-α at day 6 through to day 12 after major orthopedic surgery. Attenuated TNF-α release may contribute to an increased postoperative susceptibility to gram-negative sepsis.

Investigation of Lipopolysaccharide Receptor Expression on Human Monocytes after Major Orthopaedic Surgery

“…In previous studies [8,25] , we have shown that a major musculoskeletal trauma in form of a total hip replacement causes depression of the ability of leucocytes to respond to LPS-induced release of TNF-␣ 6, 9, and 12 days but not 1 day after surgery. TNF-␣ is a pivotal mediator of normal immune function, and disability to produce TNF-␣ is associated with an increased risk of infection [16] .…”

“…In a previous study [25] , we have shown that in patients undergoing total hip prosthesis surgery there is a reduced leucocyte capacity to release TNF-␣ on LPS stimulation 6, 9, and 12 days postoperatively, even though there was no such depression of the innate immune system on day 1 after surgery. We hypothesized, therefore, that a mechanism behind the cell-mediated hyporesponsiveness to LPS after musculoskeletal trauma is an altered expression of the LPS receptor complex.…”

Local and systemic chemokine patterns in a human musculoskeletal trauma model

“…To prevent the interference of different pathophysiological events, we searched for a reproducible, standardised and isolated skeletal muscle injury in humans. Elective hip replacement is a model with adequate trauma, postoperative hyper-inflammation, and hypo-inflammation in the later postoperative course comparable to trauma patients [20][21][22]. The present study, therefore, focussed on the early local and systemic changes of a set of chemokines and their impact on the leukocytes.…”