Cytokines in Surgical Trauma: Cholecystectomy as an Example

Reber, P. U.; Andrén-Sandberg,; Schmied, BM; Büchler, M W

doi:10.1159/000018600

Cited by 26 publications

(15 citation statements)

References 52 publications

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“…We chose to study patients undergoing laparoscopic cholecystectomy because these patients represent a relatively homogenous group with, therefore, a more reproducible physiological response in whom we would be likely to detect any influence of GH treatment. The surgery had a relatively minor effect on cytokine production, inducing a rise in IL-6 levels at 24 h and a fall in TNF␣ at 24 h. These results are broadly similar to previous observations in this patient group (19,20), although in one study TNF␣ levels were higher at 24 h (21). The finding that GH had no effect on the cytokine response to surgery is consistent with results in another patient group.…”

Section: Discussionsupporting

confidence: 89%

“…For example, different changes are seen in patients undergoing open vs. laparoscopic cholecystectomy (19). We chose to study patients undergoing laparoscopic cholecystectomy because these patients represent a relatively homogenous group with, therefore, a more reproducible physiological response in whom we would be likely to detect any influence of GH treatment.…”

Section: Discussionmentioning

confidence: 99%

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High-Dose Growth Hormone Does Not Affect Proinflammatory Cytokine (Tumor Necrosis Factor-α, Interleukin-6, and Interferon-γ) Release from Activated Peripheral Blood Mononuclear Cells or after Minimal to Moderate Surgical Stress*

Zarkesh-Esfahani

Kolstad

Metcalfe

et al. 2000

The Journal of Clinical Endocrinology &Amp; Metabolism

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High-dose GH therapy, with GH doses 10 -20 times the normal replacement dose for GH-deficient adults, has been used as an anticatabolic agent in a number of different patient groups. A recent study, however, has shown an increase in mortality in critically ill patients treated with high-dose GH. The increased mortality was associated with multiorgan failure, septic shock, and uncontrolled infection, suggesting that GH may have altered the immune response. The GH receptor and GH are both expressed in peripheral blood mononuclear cells (PBMCs); thus, GH could act as either an endocrine or an autocrine modulator of the immune response. We have examined the hypothesis that high-dose GH therapy may induce proinflammatory cytokines, which are implicated in septic shock. To do this we measured cytokine production by PBMCs incubated in conditions that simulated high-dose GH therapy, and we measured cytokine levels in patients undergoing laparoscopic cholecystectomy who were randomized to receive either high-dose GH therapy (13 IU/m 2 ⅐day) or placebo.To confirm the biological activity of GH in our cell culture system we used a Stat5 functional assay. In this assay GH induced a bellshaped curve, with a maximal response at GH levels between 100-1000 ng/mL. PBMCs from healthy volunteers were incubated with GH in doses from 1-1000 ng/mL for 6 -72 h under resting conditions and after activation with endotoxin and the mixed lymphocyte reaction. Studies were repeated with PBMCs from six individuals using a GH dose of 100 ng/mL (the level of GH found after high-dose GH therapy) and an endotoxin dose that gave a submaximal response (0.01 ng/mL). GH had no effect on cell proliferation or the production of tumor necrosis factor-␣ (TNF␣), interleukin-6 (IL-6), or interferon-␥ (IFN␥). In patients undergoing laparoscopic cholecystectomy there was a time-related effect of surgery on cytokine levels. There was a rise in IL-6 and a fall in TNF␣ at 24 h after surgery; however, high-dose GH therapy had no effect on the cytokine response. We considered the possibility that endogenous GH production by PBMCs could influence the cytokine response in activated PBMCs; however, incubation of PBMCs in the presence of the GH receptor antagonist, B2036, had no effect on TNF␣, IL-6, or IFN␥ production by PBMCs in either the mixed lymphocyte reaction or when activated by endotoxin.These results suggest that high-dose GH therapy does not alter the proinflammatory cytokine response to surgery or endotoxin. The results do not exclude an effect of GH on the immune response, but they suggest that the mortality seen in critically ill patients may be due to factors other than immune modulation. (J Clin Endocrinol Metab 85: 3383-3390, 2000)

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Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 99%

High-Dose Growth Hormone Does Not Affect Proinflammatory Cytokine (Tumor Necrosis Factor-α, Interleukin-6, and Interferon-γ) Release from Activated Peripheral Blood Mononuclear Cells or after Minimal to Moderate Surgical Stress*

Zarkesh-Esfahani

Kolstad

Metcalfe

et al. 2000

The Journal of Clinical Endocrinology &Amp; Metabolism

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“…Unfortunately, this kind of response in not always beneficial for the recovering patient because hyperproduction of inflammatory mediators can interfere with healing, affecting morbidity or cause a systemic inflammatory response syndrome affecting mortality. 11 Different cytokines have been recognized to be involved primarily in the stress response to surgery. TNF-␣ is secreted by activated macrophages with some metabolic effects on lipid metabolism, it also activates IL-6 production.…”

Section: Discussionmentioning

confidence: 99%

Melatonin reduces oxidative stress in surgical neonates

Gitto

Romeo

Reíter

et al. 2004

Journal of Pediatric Surgery

157

120

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“…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%

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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Cytokines in Surgical Trauma: Cholecystectomy as an Example

Cited by 26 publications

References 52 publications

High-Dose Growth Hormone Does Not Affect Proinflammatory Cytokine (Tumor Necrosis Factor-α, Interleukin-6, and Interferon-γ) Release from Activated Peripheral Blood Mononuclear Cells or after Minimal to Moderate Surgical Stress*

High-Dose Growth Hormone Does Not Affect Proinflammatory Cytokine (Tumor Necrosis Factor-α, Interleukin-6, and Interferon-γ) Release from Activated Peripheral Blood Mononuclear Cells or after Minimal to Moderate Surgical Stress*

Melatonin reduces oxidative stress in surgical neonates

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

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