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@ARTICLE{Merbecks:156843,
      author       = {M. B. Merbecks and V. C. Ziesenitz and T. Rubner$^*$ and N.
                      Meier and B. Klein and H. Rauch and P. Saur and N. Ritz and
                      T. Loukanov and S. Schmitt$^*$ and M. Gorenflo},
      title        = {{I}ntermediate monocytes exhibit higher levels of {TLR}2,
                      {TLR}4 and {CD}64 early after congenital heart surgery.},
      journal      = {Cytokine},
      volume       = {133},
      issn         = {1043-4666},
      address      = {Oxford ˜[u.a.]œ},
      publisher    = {Elsevier},
      reportid     = {DKFZ-2020-01160},
      pages        = {155153},
      year         = {2020},
      note         = {Volume 133, September 2020, 155153},
      abstract     = {Congenital heart surgery with cardiopulmonary bypass (CPB)
                      initiates an immune response which frequently leads to organ
                      dysfunction and a systemic inflammatory response.
                      Complications associated with exacerbated immune responses
                      may severely impact the postoperative recovery. The
                      objective was to describe the characteristics of monocyte
                      subpopulations and neutrophils at the level of pattern
                      recognition receptors (PRR) and the cytokine response after
                      CPB in infants.An observational cohort study was conducted
                      between June 2016 and June 2017 of infants < 2 years of
                      age, electively admitted for surgical correction of
                      acyanotic congenital heart defects using CPB. Fourteen blood
                      samples were collected sequentially and processed
                      immediately during and up to 48 h following cardiac surgery
                      for each patient. Flow cytometry analysis comprised
                      monocytic and granulocytic surface expression of CD14, CD16,
                      CD64, TLR2, TLR4 and Dectin-1 (CLEC7A). Monocyte
                      subpopulations were further defined as classical
                      (CD14++/CD16-), intermediate (CD14++/CD16+) and nonclassical
                      (CD14+/CD16++) monocytes. Plasma concentrations of 14
                      cytokines, including G-CSF, GM-CSF, IL-1β, IL-1RA, IL-4,
                      IL-6, IL-8, IL-10, IL-12p40, IL-12p70, TNF-α, IFN-γ,
                      MIP-1β (CCL4) and TGF-β1, were measured using multiplex
                      immunoassay for seven points in time.Samples from 21 infants
                      (median age 7.4 months) were analyzed by flow cytometry and
                      from 11 infants, cytokine concentrations were measured.
                      Classical and intermediate monocytes showed first receptor
                      upregulation with an increase in CD64 expression four hours
                      post CPB. CD64-expression on intermediate monocytes almost
                      tripled 48 h post CPB (p < 0.0001). TLR4 was only
                      increased on intermediate monocytes, occurring 12 h post
                      CPB (p = 0.0406) along with elevated TLR2 levels
                      (p = 0.0002). TLR4 expression on intermediate monocytes
                      correlated with vasoactive-inotropic score (rs = 0.642,
                      p = 0.0017), duration of ventilation (rs = 0.485,
                      p = 0.0259), highest serum creatinine (rs = 0.547,
                      p = 0.0102), postsurgical transfusion (total volume per kg
                      bodyweight) (rs = 0.469, p = 0.0321) and lowest mean
                      arterial pressure (rs = -0.530, p = 0.0135).
                      Concentrations of IL-10, MIP-1β, IL-8, G-CSF and IL-6
                      increased one hour post CPB. Methylprednisolone
                      administration in six patients had no significant influence
                      on the studied surface receptors but led to lower IL-8 and
                      higher IL-10 plasma concentrations.Congenital heart surgery
                      with CPB induces a systemic inflammatory process including
                      cytokine response and changes in PRR expression.
                      Intermediate monocytes feature specific inflammatory
                      characteristics in the 48 h after pediatric CPB and TLR4
                      correlates with poorer clinical course, which might provide
                      a potential diagnostic or even therapeutic target.},
      cin          = {W220},
      ddc          = {570},
      cid          = {I:(DE-He78)W220-20160331},
      pnm          = {319H - Addenda (POF3-319H)},
      pid          = {G:(DE-HGF)POF3-319H},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:32554157},
      doi          = {10.1016/j.cyto.2020.155153},
      url          = {https://inrepo02.dkfz.de/record/156843},
}