Reduced Capacity of Whole Blood Leucocytes to Express Tumour Necrosis Factor-α and Interleukin-10 following Major Orthopaedic Surgery

Reikeraas, O.; Sun, Juan; Krohn, Claus Danckert; Wang, J.E.; Aasen, A O

doi:10.1159/000087865

Cited by 10 publications

(13 citation statements)

References 47 publications

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“…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] .…”

Section: Discussionmentioning

confidence: 93%

“…Within the cytokine network, tumour necrosis factor alpha (TNF-␣ ) and interleukin (IL)-1 ␤ stimulate the production and release of other cytokines, including IL-6, which markedly peak 4-48 h after surgery [5,6] . Following the pro-inflammatory reaction, anti-inflammatory mediators, like IL-4, IL-10, and IL-13, are produced to avoid autodestructive effects of immunocompetent cells [7,8] . IL-10 has been suggested as a potential candidate for in-duction of the compensatory anti-inflammatory response syndrome, because it strongly suppresses the pro-inflammatory cytokine synthesis in vivo and in vitro [9][10][11] .…”

Section: Introductionmentioning

confidence: 99%

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

Daniel

Shegarfi²,

Rolstad³

et al. 2007

Eur Surg Res

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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.

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Section: Discussionmentioning

confidence: 93%

Section: Introductionmentioning

confidence: 99%

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

Daniel

Shegarfi²,

Rolstad³

et al. 2007

Eur Surg Res

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“…34 It has been shown that hip arthroplasty causes depression of the leukocytes ability to respond to LPS-induced release of TNF-a throughout the first postoperative week. 14 The responsiveness of whole blood to endotoxin stimulation is an indicator of leukocyte function, and determination of the cytokine production capacity from whole blood cultures stimulated with LPS ex vivo provides an estimate of the patient's inflammatory capacity. Therefore, we used the ex vivo responsiveness of human whole blood leukocytes to LPS stimulation as a method for investigating the It is well accepted that trauma leads to diminished cell-mediated immunity which may render the patient particularly susceptible to septic complications.…”

Section: Discussionmentioning

confidence: 99%

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

Reikerås

Sun

Wang

et al. 2007

Journal Orthopaedic Research

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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-a 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-a and IL-10 in whole blood. Addition of preoperative, postoperative, and day-1 postoperative serum did not alter the LPS-induced release of TNF-a as compared to saline. In the presence of serum from postoperative day 6, however, the expression of TNF-a was significantly reduced as compared to saline and preoperative serum (p ¼ 0.021 and 0.008, respectively). Neither of the serum samples altered the release of IL-10. PGE2 was significantly (p ¼ 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-a release. The potent TNF-a inhibitory activity found at day 6 after injury correlated with increased levels of PGE2 and indicates cellmediated hyporesponsiveness to a second stimulus. ß

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“…The level of significance was set at 0.05. Based on our previous study [7,9] , we used Sample Power 2.0 (SPSS, Chicago, Ill., USA) to estimate the number of 7 patients for inclusion.…”

Section: Methodsmentioning

confidence: 99%

“…To reduce the confounding factors associated in accidental trauma, the study was performed in patients undergoing a major musculoskeletal injury in the form of total hip replacement. We used LPS stimulation of whole blood as an ex vivo model of inflammation [6,7] . Although this ex vivo system cannot accurately depict inflammatory processes in the whole individual, it is of considerable relevance with respect to in vivo endotoxin exposure.…”

Section: Introductionmentioning

confidence: 99%

Immune Modulation after Total Hip Surgery

Daniel

Sun²,

Krohn³

et al. 2007

Eur Surg Res

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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.

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Reduced Capacity of Whole Blood Leucocytes to Express Tumour Necrosis Factor-α and Interleukin-10 following Major Orthopaedic Surgery

Cited by 10 publications

References 47 publications

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

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

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

Immune Modulation after Total Hip Surgery

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