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

Reikerås, Olav; Sun, Juan; Wang, Jacob E.; Aasen, Ansgar O.

doi:10.1002/jor.20454

Cited by 10 publications

(4 citation statements)

References 41 publications

(36 reference statements)

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“…[9][10][11][12] In patients, inflammatory molecules such as TNF-a and interleukins appear in CSF within 12 hours after major surgery. 4,[13][14][15] Although such clinical observations are in line with a series of experimental studies, 2,3,8 the time course pattern beyond the immediate postsurgery phase of immune activation within the human CNS is unknown, and how the systemic pro-and anti-inflammatory response [16][17][18] is associated with cognitive performance is largely unexplored.…”

mentioning

confidence: 79%

“…The depressed ex vivo response to LPS in blood from surgical patients is in line with previously described peripheral immune cell tolerance, typically triggered by anti-inflammatory mediators such as IL-10 and PGE 2 causing dampening of peripheral immune cell reactivity within a duration of up to 5 days after the proinflammatory triggering event. 17,[57][58][59][60] In addition to this autocrine peripheral regulation, there might be an additive neuroimmunological link between the CNS and the peripheral immune system as represented by the cholinergic anti-inflammatory reflex pathway, previously described by Tracey. 61 The analysis of [ 11 C]PBR28 binding and cognitive test data revealed an association between the increase in brain immune activity and an impairment in performance of the highly sensitive Stroop Color-Word Test.…”

Section: Forsberg Et Al: Brain After Abdominal Surgerymentioning

confidence: 99%

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The immune response of the human brain to abdominal surgery

Forsberg

Červenka

Fagerlund

et al. 2017

Annals of Neurology

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Objective: Surgery launches a systemic inflammatory reaction that reaches the brain and associates with immune activation and cognitive decline. Although preclinical studies have in part described this systemic-to-brain signaling pathway, we lack information on how these changes appear in humans. This study examines the short-and longterm impact of abdominal surgery on the human brain immune system by positron emission tomography (PET) in relation to blood immune reactivity, plasma inflammatory biomarkers, and cognitive function. Methods: Eight males undergoing prostatectomy under general anesthesia were included. Prior to surgery (baseline), at postoperative days 3 to 4, and after 3 months, patients were examined using [ 11 C]PBR28 brain PET imaging to assess brain immune cell activation. Concurrently, systemic inflammatory biomarkers, ex vivo blood tests on immunoreactivity to lipopolysaccharide (LPS) stimulation, and cognitive function were assessed. Results: Patients showed a global downregulation of gray matter [ 11 C]PBR28 binding of 26 6 26% (mean 6 standard deviation) at 3 to 4 days postoperatively compared to baseline (p 5 0.023), recovering or even increasing after 3 months. LPS-induced release of the proinflammatory marker tumor necrosis factor-a in blood displayed a reduction (41 6 39%) on the 3rd to 4th postoperative day, corresponding to changes in [ 11 C]PBR28 distribution volume. Change in Stroop Color-Word Test performance between postoperative days 3 to 4 and 3 months correlated to change in [ 11 C]PBR28 binding (p 5 0.027). Interpretation: This study translates preclinical data on changes in the brain immune system after surgery to humans, and suggests an interplay between the human brain and the inflammatory response of the peripheral innate immune system. These findings may be related to postsurgical impairments of cognitive function. ANN NEUROL 2017;81:572-582 A growing body of evidence suggests that surgical trauma launches a systemic inflammatory response that ultimately reaches and activates the intrinsic immune system of the brain. [1][2][3][4] Triggered by surgery-induced damage-associated molecular patterns (DAMPs), an array of proinflammatory mediators and activated blood-borne immune cells orchestrate a rapid spread of this systemic response to the central nervous system (CNS), with inflammatory markers detectable in human cerebrospinal fluid (CSF) within 12 hours. [4][5][6][7] In surgical rodent models, this periphery-to-brain pathway seems critically dependent on NF-jB and proinflammatory cytokine signaling (eg, tumor necrosis factor-a [TNF-a]) associated with a shortlasting disruption of blood-brain barrier integrity, 2,3,8 migration of peripheral macrophages into the CNS, and subsequent hippocampal neuronal dysfunction and cognitive impairment. 8 In addition to an acute and transient response, often referred to as a syndrome of sickness behavior including fatigue, anorexia, and fever, surgery-induced immune activation may be associated with prolonged impairments in learning,...

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confidence: 79%

Section: Forsberg Et Al: Brain After Abdominal Surgerymentioning

confidence: 99%

The immune response of the human brain to abdominal surgery

Forsberg

Červenka

Fagerlund

et al. 2017

Annals of Neurology

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“…The mechanisms underlying posttraumatic immune depression with reduced leukocyte function is not clear. At the event of musculoskeletal trauma, bacterial infections are not present, and interest has focused on the release of mediators in the serum that might impair leukocyte function [67]. Recently it was found that tissue-derived factors circulating in the patients' serum after injury suppress monocyte function and, therefore, might cause immune suppression [68].…”

Section: Endotoxin Tolerancementioning

confidence: 99%

Immune depression in musculoskeletal trauma

Reikerås

2010

Inflamm. Res.

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The immune responses after musculoskeletal trauma are physiological reactions of the organism to restore homeostasis. An imbalance between the early systemic inflammatory response syndrome and the later compensatory anti-inflammatory response syndrome may be responsible for organ dysfunction and increased susceptibility to infections. Cytokines are known to be integral components of the immune response, and the balance or imbalance of the different cytokines partly controls the clinical course in the patients. The major pro-inflammatory cytokines include tumor necrosis factor-alpha (TNF-a), interleukin-1beta (IL-1b), IL-6, and IL-8. These cytokines are predominantly produced by monocytes and macrophages, they mediate overlapping effects, and their actions can be additive. TNF-a and IL-1b are early regulators of the immune response, and both induce the release of secondary pro-inflammatory cytokines. IL-10 is an anti-inflammatory cytokine which reduces the synthesis of pro-inflammatory mediators. The extent of traumatic damage correlates with the immunological changes and determines a graded depression of leucocytes to express cytokines on edotoxin exposure. Correspondingly, it has become clinically evident that in unstable traumatised patients, the recommendation today is damage control orthopaedics, i.e. initial stabilisation of long bone fractures by external fixation followed by definitive stabilisation at about 1 week.

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“…A recent study also examined the relationship between the levels of PGE2 and TNF-␣ in vivo. It was found that increased PGE2 levels in postoperative patient serum correlated to a potent inhibitory effect on TNF-␣ expression (30). Our current study and the previously mentioned studies repeatedly showed that PGE2 may have an inhibitory effect on the expression of TNF-␣.…”

Section: Discussionmentioning

confidence: 57%