Home About us Editorial board Ahead of print Current issue Search Archives Submit article Instructions Subscribe Contacts Login 
  • Users Online: 10850
  • Home
  • Print this page
  • Email this page


 
 Table of Contents  
BRIEF REPORTS: REPUBLICATION
Year : 2017  |  Volume : 3  |  Issue : 3  |  Page : 112-114

Correlation between CCL20 and serum glucose in postoperative coronary bypass patient: A call for further investigation


1 Department of Medical Microbiology and Immunology, University of Toledo Medical Center, Toledo; Department of Anesthesiology, The Ohio State University Medical Center; Columbus, OH, USA
2 Department of Biomedical Engineering, University of Toledo College of Engineering, Toledo, OH, USA
3 Department of Medical Microbiology and Immunology, University of Toledo Medical Center, Toledo, OH, USA
4 Department of Anesthesiology, The Ohio State University Medical Center, Columbus, OH, USA
5 Department of Surgery, Division of Critical Care, Trauma, and Burn, The Ohio State University Medical Center, Columbus, OH, USA

Date of Web Publication21-Apr-2017

Correspondence Address:
Thomas J Papadimos
Department of Anesthesiology, The Ohio State University Medical Center, Columbus, OH 43210
USA
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/IJAM.IJAM_101_16

Rights and Permissions
  Abstract 


Insulin administration during cardiopulmonary bypass grafting and in the perioperative period has been shown to lower tumor necrosis factor-α, interleukin-6 (IL-6), and IL-8 levels, which are considered to be mediators of immunity and inflammation. It is not known whether perioperative hyperglycemia attenuates the action of lymphocyte attracting chemokines such as (CC-motif) ligand 20 (CCL20), also known as macrophage inflammatory protein 3; or liver activation regulated chemokine. CCL20 is a selective chemoattractant for immature dendritic cells, effector/memory T lymphocytes and naïve B cells, and is recognized as a critical regulator of both innate and acquired immunity. In this report, we describe our preliminary findings of the interaction between serum blood glucose and CCL20. Specifically, we report an increase in CCL20 temporally associated with improving glycemic control in a diabetic patient undergoing intensive insulin therapy after open heart surgery.
The following core competencies are addressed in this article: Medical knowledge.
Republished with permission from: Papadimos TJ, Pappada SM, Lather JD, Bazalitski V, Stawicki SP, Cameron BD, Pan ZK. Correlation between CCL20 and serum glucose in postoperative coronary bypass patient: A call for further investigation. OPUS 12 Scientist 2010; 4(1):1-2.

Keywords: Cardiac surgery, chemokines, critical care, cytokines, diabetes, glucose, wound healing


How to cite this article:
Papadimos TJ, Pappada SM, Lather JD, Bazalitski V, Stawicki SP, Cameron BD, Pan Z K. Correlation between CCL20 and serum glucose in postoperative coronary bypass patient: A call for further investigation. Int J Acad Med 2017;3, Suppl S1:112-4

How to cite this URL:
Papadimos TJ, Pappada SM, Lather JD, Bazalitski V, Stawicki SP, Cameron BD, Pan Z K. Correlation between CCL20 and serum glucose in postoperative coronary bypass patient: A call for further investigation. Int J Acad Med [serial online] 2017 [cited 2020 Oct 30];3, Suppl S1:112-4. Available from: https://www.ijam-web.org/text.asp?2017/3/3/112/204944




  Introduction Top


In postoperative cardiac surgery patients, hyperglycemia has been associated with increased levels of tumor necrosis factor-α (TNF-α) in peripheral blood.[1],[2],[3],[4] Insulin administration during cardiopulmonary bypass grafting (CABG) and the perioperative period has been shown to lower TNF-α, interleukin-6 (IL-6), and IL-8 levels, which are considered to be mediators of immunity and inflammation.[5] It is not known whether perioperative hyperglycemia attenuates the action of lymphocyte attracting chemokines such as CCL20 [(CC-motif) ligand 20], also known as macrophage inflammatory protein 3; or liver activation regulated chemokine. CCL20 is a selective chemoattractant for immature dendritic cells, effector/memory T lymphocytes and naïve B cells, and is recognized as a critical regulator of both innate and acquired immunity.[6]

CCL20 is involved in the formation and function of mucosal lymphoid tissues via chemoattraction of lymphocytes and dendritic cells to epithelial cells surrounding these tissues. It binds and activates chemokine receptor CCR6. CCL20 is upregulated in the wound healing of mouse gingiva and in postoperative total hip arthroplasties.[7],[8] It is also induced in human keratinocytes by electric fields of 100-300 mV/mm and is upregulated by human gingival fibroblasts on stimulation with cytokines and bacterial endotoxin. CCL20 is thought to recruit immature dendritic cells to skin wound sites.[7],[9] In this report, we describe our preliminary findings related to the interaction between serum blood glucose and CCL20. Specifically, we report increasing levels of CCL20 that temporally correlated with improving glycemic control in a diabetic patient undergoing intensive insulin therapy for hyperglycemia after open heart surgery.


  Case Report Top


An 82-year-old hypertensive, diabetic, female had undergone three-vessel coronary artery bypass grafting. She was a participant in an Institutional Review Board-approved protocol in which, in addition to glucose point-of-care testing (nurses performing finger sticks), her interstitial tissue was sampled by a continuous glucose monitoring system (Medtronic Diabetes CGMS Ipro ®, Northridge, CA). The patient was initially placed on an insulin sliding scale regimen with subcutaneous injections, with early therapeutic failure (i.e., glucose level 244 mg/dl shortly after initiation of therapy). The decision was made to begin insulin infusion with additional glucose level sampling via point-of-care testing.

After patient consent for additional sampling was granted, five 3-milliliter blood samples were collected at 120–150 min intervals (over 525 min) with measurements of CCL20 and TNF-α by enzyme linked immunosorbent assay, and nuclear factor-κβ by western blot. The results are listed in [Table 1]. The initial sample was drawn before the insulin infusion was started. As can be seen, serum levels of CCL20 demonstrated an inverse relationship to both serum glucose and to TNF-α levels.
Table 1: Concentrations of CCL20 and TNF-a in consecutive blood samples

Click here to view



  Discussion Top


These results bring forth interesting questions regarding the relationship of insulin and/or glycemic control and the behavior of serum CCL20 levels. Our finding may be of importance in the areas immunomodulation and wound healing. Furnary et al. established that continuous insulin infusions decreased deep sternal wound infection rates in diabetic CABG patients despite the fact that the interventional group had more morbid obesity and increased rates of intrathoracic conduit placement.[3] Estrada et al. showed that hyperglycemia in any CABG patient could result in longer hospitalization and increased costs.[2] This work was followed by findings that high-dose insulin therapy attenuates inflammation in the early postoperative period as demonstrated by decreased levels of IL6, IL8, and TNF-α [5], and that TNF-α increases cell apoptosis, and impairs wound healing in diabetic patients.[4] Hosokawa et al. found that in periodontal tissue IL8, TNF-α, and Escherichia coli lipopolysaccharide induce CCL20.[9] These cytokines may universally induce CCL20 in humans. It is important to note that same investigators also demonstrated that vascular endothelial growth factor (VEGF) levels were higher in cultures treated with CCL20. VEGF serves as a cellular signal that stimulates new blood vessel growth and enhances oxygen supply to tissues when there is inadequate circulation. In addition, Buvanendran et al. have recently demonstrated that CCL20 gene expression, from wound samples collected 24 h postoperatively, is upregulated after total hip arthroplasty, although its role (other than being a strong lymphocyte chemoattractant and weak recruiter of neutrophils) could not be elucidated in that study.[8]


  Conclusions Top


The above case report suggests that insulin therapy and improved glycemic control may be associated with decreased serum TNF-α levels and increased CCL20 levels. In postoperative cardiac surgery patients, this may be of importance because of the known relationship between hyperglycemia and impaired wound healing, among other factors. Specific areas for additional research include the potential role of CCL20 in postoperative wound healing and immunity (especially in diabetic patients), as well as the clarification of the signaling pathways that result in the upregulation of CCL20 (specifically through the activation of toll-like receptor 2 and TRAF6, MyD88, and NF-Kβ).

Acknowledgement

Justifications for re-publishing this scholarly content include: (a) The phasing out of the original publication after a formal merger of OPUS 12 Scientist with the International Journal of Academic Medicine and (b) Wider dissemination of the research outcome(s) and the associated scientific knowledge.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Dellinger EP. Preventing surgical-site infections: The importance of timing and glucose control. Infect Control Hosp Epidemiol 2001;22:604-6.  Back to cited text no. 1
    
2.
Estrada CA, Young JA, Nifong LW, Chitwood WR Jr. Outcomes and perioperative hyperglycemia in patients with or without diabetes mellitus undergoing coronary artery bypass grafting. Ann Thorac Surg 2003;75:1392-9.  Back to cited text no. 2
    
3.
Furnary AP, Zerr KJ, Grunkemeier GL, Starr A. Continuous intravenous insulin infusion reduces the incidence of deep sternal wound infection in diabetic patients after cardiac surgical procedures. Ann Thorac Surg 1999;67:352-60.  Back to cited text no. 3
    
4.
Liu R, Bal HS, Desta T, Behl Y, Graves DT. Tumor necrosis factor-alpha mediates diabetes-enhanced apoptosis of matrix-producing cells and impairs diabetic healing. Am J Pathol 2006;168:757-64.  Back to cited text no. 4
    
5.
Albacker T, Carvalho G, Schricker T, Lachapelle K. High-dose insulin therapy attenuates systemic inflammatory response in coronary artery bypass grafting patients. Ann Thorac Surg 2008;86:20-7.  Back to cited text no. 5
    
6.
Schutyser E, Struyf S, Van Damme J. The CC chemokine CCL20 and its receptor CCR6. Cytokine Growth Factor Rev 2003;14:409-26.  Back to cited text no. 6
    
7.
McGrory K, Flaitz CM, Klein JR. Chemokine changes during oral wound healing. Biochem Biophys Res Commun 2004;324:317-20.  Back to cited text no. 7
    
8.
Buvanendran A, Mitchell K, Kroin JS, Iadarola MJ. Cytokine gene expression after total hip arthroplasty: Surgical site versus circulating neutrophil response. Anesth Analg 2009;109:959-64.  Back to cited text no. 8
    
9.
Hosokawa Y, Hosokawa I, Ozaki K, Nakae H, Matsuo T. Increase of CCL20 expression by human gingival fibroblasts upon stimulation with cytokines and bacterial endotoxin. Clin Exp Immunol 2005;142:285-91.  Back to cited text no. 9
    



 
 
    Tables

  [Table 1]



 

Top
 
 
  Search
 
Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
Access Statistics
Email Alert *
Add to My List *
* Registration required (free)

 
  In this article
Abstract
Introduction
Case Report
Discussion
Conclusions
References
Article Tables

 Article Access Statistics
    Viewed1228    
    Printed73    
    Emailed0    
    PDF Downloaded15    
    Comments [Add]    

Recommend this journal


[TAG2]
[TAG3]
[TAG4]