<i>In vivo </i>application of Granulocyte-Macrophage Colony-stimulating Factor enhances postoperative qualitative monocytic function

Lachmann, Gunnar; Kurth, Johannes; Haefen, Clarissa von; Yuerek, Fatima; Wernecke, Klaus‐Dieter; Spies, Claudia

doi:10.7150/ijms.18288

Cited by 5 publications

(5 citation statements)

References 19 publications

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“…Basic patient characteristics, intraoperative- and outcome parameters are shown in Table 1 . Some of the results were already shown to analyze group differences after postoperative immune stimulation 23 .…”

Section: Resultsmentioning

confidence: 99%

“…This retrospective subgroup analysis of a previously published study of our research group 22 , 23 investigated innate and acquired immune cells as well as monocytic and T cell immune function during severe postoperative immune suppression (mHLA-DR ≤ 10,000 antigens per cell on pod1) that were measured in 10 out of 20 patients of the placebo group of the bigger cohort until pod5 after elective esophageal or pancreatic resection (measurement had to be stopped after 10 patients for economic reasons, no selection of the patients; Figure 1 ). All patients received guideline-based anesthesiological and surgical treatment according to our standard operating procedures 24 .…”

Section: Methodsmentioning

confidence: 99%

“…Cell phenotyping was performed by flow cytometry/fluorescence-activated cell sorting (FACS) on a FACSCalibur™ using CELLQuest™ Software (BD Biosciences). LPS-induced monocytic tumor necrosis factor alpha (TNF-α) and Interleukin (IL)-10 secretion ex vivo as well as Concanavalin A (Con A)-induced interferon gamma (IFN-γ), TNF-α, IL-2, IL-4, IL-5 and IL-10 release were determined as described earlier 23 .…”

Section: Methodsmentioning

confidence: 99%

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Innate immunity recovers earlier than acquired immunity during severe postoperative immunosuppression

Lachmann¹,

Haefen²,

Kurth³

et al. 2018

Int. J. Med. Sci.

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Background: Postoperative immune suppression, particularly a loss of cell-mediated immunity, is commonly seen after surgery and is associated with worse outcome, i.e. delayed wound healing, infections, sepsis, multiple-organ failure and cancer recurrence. However, the recovery of immune cells focusing on differences between innate and acquired immunity during severe postoperative immunosuppression is not investigated. Methods: In this retrospective randomized controlled trial (RCT) subgroup analysis, 10 postoperatively immune suppressed patients after esophageal or pancreatic resection were analyzed. Innate and acquired immune cells, the expression of human leukocyte antigen-D related on monocytes (mHLA-DR), lipopolysaccharide (LPS)-induced monocytic TNF-α and IL-10 secretion ex vivo, Concanavalin A (Con A)-induced IFN-γ, TNF-α, IL-2, IL-4, IL-5 and IL-10 release were measured preoperatively (od) until day 5 after surgery (pod5). Recovery of immune cells was defined by a significant decrease respectively increase after a significant postoperative alteration. Statistical analyses were performed using nonparametric statistical procedures. Results: Postoperative alterations of innate immune cells recovered on pod2 (eosinophils), pod3 (neutrophils) and pod5 (mHLA-DR, monocytic TNF-α and IL-10 secretion), whereas alterations of acquired immune cells (lymphocytes, T cells, T helper cells, and cytotoxic T cells) did not recover until pod5. Peripheral blood T cells showed an impaired production of the T helper (Th) 1 cytokine IFN-γ upon Con A stimulation on pod1, while Th2 specific cytokine release did not change until pod5. Conclusions: Innate immunity recovered earlier than acquired immunity during severe postoperative immunosuppression. Furthermore, we found a more anti- than pro-inflammatory T cell function on the first day after surgery, while T cell counts decreased.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Innate immunity recovers earlier than acquired immunity during severe postoperative immunosuppression

Lachmann¹,

Haefen²,

Kurth³

et al. 2018

Int. J. Med. Sci.

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“…Furthermore, GM-CSF treatment increased expression of HLA-DR on monocytes in immunosuppressed patients after surgery; GM-CSF treated group had fewer days with infection compared to placebo and influenza vaccination as a treatment [ 34 ]. A subsequent analysis of this trial showed that, in addition to increased HLA-DR, monocytes from GM-CSF treated patients showed increased release of LPS-induced TNF [ 35 ]. These results suggest a potentially clinically relevant role for the GM-CSF induction of HLA-DR.…”

Section: Discussionmentioning

confidence: 99%

The MHC class II antigen presentation pathway in human monocytes differs by subset and is regulated by cytokines

et al. 2017

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Monocytes play a critical role in the innate and adaptive immune systems, performing phagocytosis, presenting antigen, and producing cytokines. They are a heterogeneous population that has been divided in humans into classical, intermediate, and non-classical subsets, but the roles of these subsets are incompletely understood. In this study, we investigated the expression patterns of MHC class II (MHCII) and associated molecules and find that the intermediate monocytes express the highest levels of the MHC molecules, HLA-DR (tested in n = 30 samples), HLA-DP (n = 30), and HLA-DQ (n = 10). HLA-DM (n = 30), which catalyzes the peptide exchange on the MHC molecules, is also expressed at the highest levels in intermediate monocytes. To measure HLA-DM function, we measured levels of MHCII-bound CLIP (class II invariant chain peptide, n = 23), which is exchanged for other peptides by HLA-DM. We calculated CLIP:MHCII ratios to normalize CLIP levels to MHCII levels, and found that intermediate monocytes have the lowest CLIP:MHCII ratio. We isolated the different monocyte subsets (in a total of 7 samples) and analyzed their responses to selected cytokines as model of monocyte activation: two M1-polarizing cytokines (IFNγ, GM-CSF), an M2-polarizing cytokine (IL-4) and IL-10. Classical monocytes exhibit the largest increases in class II pathway expression in response to stimulatory cytokines (IFNγ, GM-CSF, IL-4). All three subsets decrease HLA-DR levels after IL-10 exposure. Our findings argue that intermediate monocytes are the most efficient constitutive antigen presenting subset, that classical monocytes are recruited into an antigen presentation role during inflammatory responses and that IL-10 negatively regulates this function across all subsets.

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“…We and others used mHLA-DR expression to stratify immune compromised patients after surgery [ 18 , 19 ] and during severe sepsis [ 20 ]. In both settings, mHLA-DR could be increased through administration of GM-CSF restoring immune function and improving outcome.…”

Section: Introductionmentioning

confidence: 99%

Smoking, Gender, and Overweight Are Important Influencing Factors on Monocytic HLA-DR before and after Major Cancer Surgery

Lachmann

Haefen

Kurth

et al. 2017

BioMed Research International

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Background Monocytic human leukocyte antigen D related (mHLA-DR) is essential for antigen-presentation. Downregulation of mHLA-DR emerged as a general biomarker of impaired immunity seen in patients with sepsis and pneumonia and after major surgery. Influencing factors of mHLA-DR such as age, overweight, diabetes, smoking, and gender remain unclear. Methods We analyzed 20 patients after esophageal or pancreatic resection of a prospective, randomized, placebo-controlled, double-blind trial (placebo group). mHLA-DR was determined from day of surgery (od) until postoperative day (pod) 5. Statistical analyses were performed using multivariate generalized estimating equation analyses (GEE), nonparametric multivariate analysis of longitudinal data, and univariate post hoc nonparametric Mann–Whitney tests. Results In GEE, smoking and gender were confirmed as significant influencing factors over time. Univariate analyses of mHLA-DR between smokers and nonsmokers showed lower preoperative levels (p = 0.010) and a trend towards lower levels on pod5 (p = 0.056) in smokers. Lower mHLA-DR was seen in men on pod3 (p = 0.038) and on pod5 (p = 0.026). Overweight patients (BMI > 25 kg/m2) had lower levels of mHLA-DR on pod3 (p = 0.039) and pod4 (p = 0.047). Conclusion Smoking is an important influencing factor on pre- and postoperative immune function while postoperative immune function was influenced by gender and overweight. Clinical trial registered with ISRCTN27114642.

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In vivo application of Granulocyte-Macrophage Colony-stimulating Factor enhances postoperative qualitative monocytic function

Cited by 5 publications

References 19 publications

Innate immunity recovers earlier than acquired immunity during severe postoperative immunosuppression

Innate immunity recovers earlier than acquired immunity during severe postoperative immunosuppression

The MHC class II antigen presentation pathway in human monocytes differs by subset and is regulated by cytokines

Smoking, Gender, and Overweight Are Important Influencing Factors on Monocytic HLA-DR before and after Major Cancer Surgery

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