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

Abstract

Background: The innate immune system is suppressed after major orthopaedic surgery, implicating a risk of septic complications. Whole-blood ex vivo testing with lipopolysaccharide (LPS) has shown a depression of the tumour necrosis factor alpha (TNF-α) production until 12 days postoperatively. As part of the innate immune system, the Toll-like receptors TLR2 and TLR4 recognize antigens from Gram-positive and Gram-negative bacteria, respectively. The receptors CD14 and CD11b are involved in the LPS receptor complex, whereas human lymphocyte antigen (HLA)-DR binds endotoxin peptides. It is still uncertain whether the expression of all these receptors changes after major surgery. Methods: In 6 patients undergoing hip arthroplasty, we investigated three times the display of TLR4, TLR2, CD14, CD11b, and HLA-DR on monocytes by fluorescence-activated cell sorting and white blood cell counts during 12 days postoperatively. At the same time, the plasma levels of interleukin (IL)-1β, IL-4, IL-6, IL-10, IL-13, and TNF-α were measured. Results: There was no significant change in the expression of TLR4, CD14, CD11b, HLA-DR, and TLR2. Monocyte count and cytokine analysis did not differ from the ones pre-operatively taken. Conclusions: After aseptic orthopaedic surgery, there is no change in the display of the LPS receptor complex on monocytes. Other mechanisms have to be investigated to gain insight into the decrease of the TNF-α production capacity postoperatively.

HLA‐DR expression and differential trafficking of monocyte subsets following low to intermediate risk surgery*

“…However, contrary to previously published observations [15], our results showed clear depression of HLA-DR expression on the monocytes of patients undergoing hip arthroplasty, and the reduction was significantly greater than in knee arthroplasty under tourniquet. Nevertheless, these differences among the groups are rather small and display poor specificity for operation type.…”

“…For monocyte HLA-DR expression to be a clinically useful predictor of postoperative complications, it needs to satisfy two criteria: (i) little depression of HLA-DR expression should occur after low-risk surgery (this indicates high specificity of HLA-DR as a marker for high risk surgery); and (ii) changes in HLA-DR should occur sufficiently early postoperatively (i.e. to facilitate appropriate alterations in patient management) [14][15][16].…”

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.…”

Innate immunity, coagulation and surgery

“…However, the impact of systemic inflammation on TLR expression on leukocytes remains unclear. Up-regulation, no change and down-regulation has been demonstrated and seems to be influenced by time, the cause of systemic inflammation (SIRS, sepsis, septic shock), the type of TLR and leukocyte (62)(63)(64)(65)(66). After Coronary artery bypass grafting (CABG) with the use of Cardiopulmonary bypass (CPB), monocytes of patients demonstrate a down-regulation of TLR2 and TLR4 expression, although on day 2 post-surgery, monocytic expression of TLR2 and TLR4 is increased (67).…”