Increased plasma interleukin 6 concentrations and exaggerated adipose tissue interleukin 6 content in severely obese patients after operative trauma

Gletsu, Nana; Lee, Edward; Zhu, Juan-Li; Khaitan, Leena; Ramshaw, Bruce; Farmer, Paul K.; Ziegler, Thomas R.; Papanicolaou, Dimitris A.; Smith, C. Daniel

doi:10.1016/j.surg.2006.01.018

Cited by 37 publications

(31 citation statements)

References 35 publications

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“…4). PGE 2 production is associated with elevated inflammation after orthopedic trauma in obesity (3,14). Elevated inflammatory cytokines can increase the production of PGE 2 within 24 h (21).…”

Section: Discussionmentioning

confidence: 99%

Impaired blood pressure recovery to hemorrhage in obese Zucker rats with orthopedic trauma

Xiang

Lu²,

Fuller

et al. 2012

American Journal of Physiology-Heart and Circulatory Physiology

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We have shown that obese Zucker rats with orthopedic trauma (OZT) exhibit a loss of arteriolar tone in skeletal muscle. We hypothesize that the loss of arteriolar tone in OZT blunts vasoconstrictor responses to hemorrhage, resulting in an impaired blood pressure recovery. Orthopedic trauma was induced with soft tissue injury and local injection of bone components in both hindlimbs in lean (LZT) and OZT (11–13 wk). One day after the orthopedic trauma, blood pressure responses following hemorrhage were measured in conscious control lean, control obese, LZT, and OZT. In another set of experiments, the spinotrapezius muscle of control and trauma animals was prepared for microcirculatory observation. Arteriolar responses to phenylephrine (PE) or hemorrhage were determined. Hemorrhage resulted in similar blood pressure responses in control animals and LZT, but the blood pressure recovery following hemorrhage was blunted in the OZT. In the spinotrapezius, OZT exhibited decreased arteriolar tone and blunted vasoconstrictor responses to PE and hemorrhage. Treatment with glibenclamide improved the blood pressure recovery in the conscious OZT and improved the arteriolar tone, and PE induced vasoconstriction in the spinotrapezius of the OZT. Thus, ATP-dependent K+ channel-mediated loss of arteriolar tone in OZT blunts the arteriolar constriction to hemorrhage, resulting in impaired blood pressure recovery.

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Section: Discussionmentioning

confidence: 99%

Impaired blood pressure recovery to hemorrhage in obese Zucker rats with orthopedic trauma

Xiang

Lu²,

Fuller

et al. 2012

American Journal of Physiology-Heart and Circulatory Physiology

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“…One day after trauma, rats were decapitated, and blood was collected to measure IL-6 levels by ELISA (R&D Systems). Circulating IL-6 levels have been previously demonstrated to be an early indicator of systemic inflammation after trauma (19,20) and are exacerbated in obese patients (21). Lung lobes were collected to measure lung edema, neutrophil counts, and myeloperoxidase (MPO) activity as we have previously described (48).…”

Section: Severe Orthopedic Trauma Protocolsmentioning

confidence: 99%

β₂-Adrenoreceptor blockade improves early posttrauma hyperglycemia and pulmonary injury in obese rats

Xiang

Mittwede

et al. 2014

American Journal of Physiology-Heart and Circulatory Physiology

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Xiang L, Lu S, Mittwede PN, Clemmer JS, Husband GW, Hester RL. ␤ 2-Adrenoreceptor blockade improves early posttrauma hyperglycemia and pulmonary injury in obese rats. Am J Physiol Heart Circ Physiol 307: H621-H627, 2014. First published June 14, 2014; doi:10.1152/ajpheart.00208.2014.-Early hyperglycemia after trauma increases morbidity and mortality. Insulin is widely used to control posttrauma glucose, but this treatment increases the risk of hypoglycemia. We tested a novel method for early posttrauma hyperglycemia control by suppressing hepatic glycogenolysis via ␤ 2-adrenoreceptor blockade [ICI-118551 (ICI)]. We have shown that, after severe trauma, obese Zucker (OZ) rats, similar to obese patients, exhibit increased acute lung injury compared with lean Zucker (LZ) rats. We hypothesized that OZ rats exhibit a greater increase in early posttrauma glucose compared with LZ rats, with the increased posttrauma hyperglycemia suppressed by ICI treatment. Orthopedic trauma was applied to both hindlimbs in LZ and OZ rats. Fasting plasma glucose was then monitored for 6 h with or without ICI (0.2 mg·kg Ϫ1 ·h Ϫ1 iv.) treatment. One day after trauma, plasma IL-6 levels, lung neutrophil numbers, myeloperoxidase (MPO) activity, and wetto-dry weight ratios were measured. Trauma induced rapid hepatic glycogenolysis, as evidenced by decreased liver glycogen levels, and this was inhibited by ICI treatment. Compared with LZ rats, OZ rats exhibited higher posttrauma glucose, IL-6, lung neutrophil infiltration, and MPO activity. Lung wet-to-dry weight ratios were increased in OZ rats but not in LZ rats. ICI treatment reduced the early hyperglycemia, lung neutrophil retention, MPO activity, and wet-to-dry weight ratio in OZ rats to levels comparable with those seen in LZ rats, with no effect on blood pressure or heart rate. These results demonstrate that ␤ 2-adrenoreceptor blockade effectively reduces the early posttrauma hyperglycemia, which is associated with decreased lung injury in OZ rats. obesity; trauma; glucose; lung injury; ␤ 2-adrenoreceptor UNINTENTIONAL INJURIES are the leading cause of mortality in individuals under 50 yr of age in the United States, with staggering medical expenses attributable to traumatic injury (10a, 43). Obese patients with severe orthopedic trauma are at a higher risk than lean patients for increased inflammation, multiorgan failure, prolonged hospital stay, and increased mortality (5,8,10,12). Although the mechanisms responsible for the increased posttrauma complications in obese patients are unclear, intensive and specific treatments have been emphasized for these patients.Posttrauma hyperglycemia has been recognized as a risk factor that exacerbates complications, organ dysfunction, and mortality (29,41,44). Several clinical studies have suggested that, in critically ill obese patients, impaired glucose homeostasis appears to be a better predictor of increased complications and mortality than body mass index (38,41,45). In addition, there is evidence that the early hyperglycemia within the f...

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“…This potential for obesity to play a causative or synergistic role in postoperative inflammation and pain has not, to our knowledge, been evaluated carefully to date. Only one report has suggested that IL-6 level is exaggerated in severely obese patients after surgery [10]. Therefore, further characterization of the inflammatory response and functional capacity of leukocytes in obese patients should be valuable in predicting postoperative course and outcomes after THA.…”

Section: Introductionmentioning

confidence: 99%

Association of Obesity With Inflammation and Pain After Total Hip Arthroplasty

Motaghedi

Bae

Memtsoudis

et al. 2014

Clinical Orthopaedics &Amp; Related Research

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Background The prevalence of obesity is increasing, and obesity often leads to degenerative joint disease requiring total hip arthroplasty (THA). Obesity is a proinflammatory state associated with an increase in chronic, low-grade inflammatory response. As such, it may augment the postoperative inflammatory response, which has been associated with postoperative pain and complications.Questions/purposes We determined whether severity of obesity was associated with (1) severity of inflammatory response, as measured by the in vivo circulating levels of cytokines and ex vivo functional reactivity of mononuclear blood cells, and (2) severity of pain, as measured by verbal pain scores and analgesic consumption, in the first 24 hours after THA. Methods We studied 60 patients (20 normal weight, 20 overweight, 20 obese) undergoing elective primary unilateral THA in this prospective cross-sectional study. Blood samples were collected for C-reactive protein and cytokine levels, including IL-1b, IL-2, IL-6, IL-8, and tumor necrosis factor a (TNF-a), from patients before and 24 hours after surgery. Cytokine response of whole blood was evaluated ex vivo with or without two standard activators, phorbol-12-myristate-13-acetate and lipopolysaccharide, using standardized blood sample from patients at 24 hours. These standard immune activators are implicated in the inflammatory response to gram-negative infection, translocation of microbial products, pathophysiology of septic shock syndrome in human, and tumor promotion. Pain response was gauged using verbal pain scores (on a 0-to 10-point scale, where 0 = no pain and 10 = worst pain) at rest and with activity at 24 hours after surgery and analgesic

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Increased plasma interleukin 6 concentrations and exaggerated adipose tissue interleukin 6 content in severely obese patients after operative trauma

Cited by 37 publications

References 35 publications

Impaired blood pressure recovery to hemorrhage in obese Zucker rats with orthopedic trauma

Impaired blood pressure recovery to hemorrhage in obese Zucker rats with orthopedic trauma

β₂-Adrenoreceptor blockade improves early posttrauma hyperglycemia and pulmonary injury in obese rats

Association of Obesity With Inflammation and Pain After Total Hip Arthroplasty

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Increased plasma interleukin 6 concentrations and exaggerated adipose tissue interleukin 6 content in severely obese patients after operative trauma

Cited by 37 publications

References 35 publications

Impaired blood pressure recovery to hemorrhage in obese Zucker rats with orthopedic trauma

Impaired blood pressure recovery to hemorrhage in obese Zucker rats with orthopedic trauma

β2-Adrenoreceptor blockade improves early posttrauma hyperglycemia and pulmonary injury in obese rats

Association of Obesity With Inflammation and Pain After Total Hip Arthroplasty

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β₂-Adrenoreceptor blockade improves early posttrauma hyperglycemia and pulmonary injury in obese rats