Thromb Haemost 2016; 116(05): 949-957
DOI: 10.1160/TH16-05-0405
Blood Cells, Inflammation and Infection
Schattauer GmbH

Monocyte subset distribution is associated with mortality in critically ill patients

Konstantin A. Krychtiuk
1   Department of Internal Medicine II - Division of Cardiology, Medical University of Vienna, Vienna, Austria
2   Ludwig Boltzmann Cluster for Cardiovascular Research, Vienna, Austria
,
Max Lenz
1   Department of Internal Medicine II - Division of Cardiology, Medical University of Vienna, Vienna, Austria
,
Lorenz Koller
1   Department of Internal Medicine II - Division of Cardiology, Medical University of Vienna, Vienna, Austria
,
Maria C. Honeder
1   Department of Internal Medicine II - Division of Cardiology, Medical University of Vienna, Vienna, Austria
,
Lisa Wutzlhofer
1   Department of Internal Medicine II - Division of Cardiology, Medical University of Vienna, Vienna, Austria
,
Chao Zhang
1   Department of Internal Medicine II - Division of Cardiology, Medical University of Vienna, Vienna, Austria
,
Lijian Chi
1   Department of Internal Medicine II - Division of Cardiology, Medical University of Vienna, Vienna, Austria
,
Gerald Maurer
1   Department of Internal Medicine II - Division of Cardiology, Medical University of Vienna, Vienna, Austria
,
Alexander Niessner
1   Department of Internal Medicine II - Division of Cardiology, Medical University of Vienna, Vienna, Austria
,
Kurt Huber
2   Ludwig Boltzmann Cluster for Cardiovascular Research, Vienna, Austria
3   3rd Medical Department, Wilhelminenhospital, Vienna, Austria
,
Johann Wojta
1   Department of Internal Medicine II - Division of Cardiology, Medical University of Vienna, Vienna, Austria
2   Ludwig Boltzmann Cluster for Cardiovascular Research, Vienna, Austria
4   Core Facilities, Medical University of Vienna, Vienna, Austria
,
Gottfried Heinz
1   Department of Internal Medicine II - Division of Cardiology, Medical University of Vienna, Vienna, Austria
,
Walter S. Speidl
1   Department of Internal Medicine II - Division of Cardiology, Medical University of Vienna, Vienna, Austria
› Author Affiliations
Financial support: This work was funded by the FWF Austrian Science Fund, Grant Number SFB-54, Cellular Mediators Linking Inflammation and Thrombosis.
Further Information

Publication History

Received: 25 May 2016

Accepted after major revision: 12 August 2016

Publication Date:
30 November 2017 (online)

Summary

Although patients admitted to an intensive care unit (ICU) suffer from various pathologies, many develop a systemic inflammatory response syndrome (SIRS). As key regulators of innate immunity, monocytes may be crucially involved in SIRS development. Monocytes can be distinguished into three subsets: Classical monocytes (CD14++CD16; CM), non-classical monocytes (CD14+CD16++CCR2; NCM) and intermediate monocytes (CD14++CD16+CCR2+; IM). The aim of this prospective, observational study was to analyse whether monocyte subset distribution is associated with 30-day survival in critically ill patients. A total of 195 consecutive patients admitted to a cardiac ICU at a tertiary-care centre were enrolled, blood was taken at admission and after 72 hours and monocyte subset distribution was analysed. Mean APACHE II score was 19.5 ± 8.1 and 30-day mortality was 25.4 %. At admission, NCM were significantly lower in non-survivors as compared to survivors [2.7 (0.4–5.5) vs 4.2 (1.6–7.5)%; p=0.012] whereas CM and IM did not differ according to 30-day survival. In contrast, 72 hours after admission, monocyte subset distribution shifted towards an increased proportion of IM [8.2 (3.9–13.2) vs 4.2 (2.3–7.9)%; p=0.003] with a concomitant decrease of CM [86.9 (78.6–89.2) vs 89.6 (84.9–93.1)%; p=0.02] in non-survivors vs survivors, respectively. NCM at day 3 were not associated with death at 30 days. These results were independent from age, gender, CRP, APACHE II score and primary diagnosis. In conclusion, circulating monocyte subsets are associated with 30-day mortality in critically ill patients. The innate immune system as reflected by monocyte subset distribution may play a major role in ICU outcome despite varying admittance pathologies.

Supplementary Material to this article is available online at www.thrombosis-online.com.

 
  • References

  • 1 Bone RC, Sprung CL, Sibbald WJ. Definitions for sepsis and organ failure. Crit Care Med 1992; 20: 724-726.
  • 2 Brun-Buisson C. The epidemiology of the systemic inflammatory response. Intensive Care Med 2000; 26 Suppl (01) S64-74.
  • 3 Bone RC, Balk RA, Cerra FB. et al. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine. Chest 1992; 101: 1644-1655.
  • 4 Bone RC. Immunologic dissonance: a continuing evolution in our understanding of the systemic inflammatory response syndrome (SIRS) and the multiple organ dysfunction syndrome (MODS). Ann Intern Med 1996; 125: 680-687.
  • 5 Ross R. Atherosclerosis--an inflammatory disease. N Engl J Med 1999; 340: 115-126.
  • 6 Passlick B, Flieger D, Ziegler-Heitbrock HW. Identification and characterisation of a novel monocyte subpopulation in human peripheral blood. Blood 1989; 74: 2527-2534.
  • 7 Belge KU, Dayyani F, Horelt A. et al. The proinflammatory CD14+CD16+DR++ monocytes are a major source of TNF. J Immunol 2002; 168: 3536-3542.
  • 8 Ziegler-Heitbrock L. The CD14+ CD16+ blood monocytes: their role in infection and inflammation. J Leukoc Biol 2007; 81: 584-592.
  • 9 Ziegler-Heitbrock L, Ancuta P, Crowe S. et al. Nomenclature of monocytes and dendritic cells in blood. Blood 2010; 116: e74-80.
  • 10 Shantsila E, Wrigley B, Tapp L. et al. Immunophenotypic characterisation of human monocyte subsets: possible implications for cardiovascular disease pa-thophysiology. J Thromb Haemost 2011; 09: 1056-1066.
  • 11 Shantsila E, Tapp LD, Wrigley BJ. et al. Receptors to interleukin-6 and adhesion molecules on circulating monocyte subsets in acute myocardial infarction. Thromb Haemost 2013; 110: 340-348.
  • 12 Shantsila E, Tapp LD, Wrigley BJ. et al. CXCR4 positive and angiogenic mono-cytes in myocardial infarction. Thromb Haemost 2013; 109: 255-262.
  • 13 Rogacev KS, Seiler S, Zawada AM. et al. CD14++CD16+ monocytes and cardiovascular outcome in patients with chronic kidney disease. Eur Heart J 2011; 32: 84-92.
  • 14 Rogacev KS, Cremers B, Zawada AM. et al. CD14++CD16+ monocytes independently predict cardiovascular events: a cohort study of 951 patients referred for elective coronary angiography. J Am Coll Cardiol 2012; 60: 1512-1520.
  • 15 Fingerle-Rowson G, Auers J, Kreuzer E. et al. Expansion of CD14+CD16+ monocytes in critically ill cardiac surgery patients. Inflammation 1998; 22: 367-379.
  • 16 Skrzeczynska J, Kobylarz K, Hartwich Z. et al. CD14+CD16+ monocytes in the course of sepsis in neonates and small children: monitoring and functional studies. Scand J Immunol 2002; 55: 629-638.
  • 17 Fingerle G, Pforte A, Passlick B. et al. The novel subset of CD14+/CD16+ blood monocytes is expanded in sepsis patients. Blood 1993; 82: 3170-3176.
  • 18 Le Gall JR, Lemeshow S, Saulnier F. A new Simplified Acute Physiology Score (SAPS II) based on a European/North American multicentre study. J Am Med Assoc 1993; 270: 2957-2963.
  • 19 Knaus WA, Draper EA, Wagner DP. et al. APACHE II: a severity of disease classification system. Crit Care Med 1985; 13: 818-829.
  • 20 Vincent JL, Moreno R, Takala J. et al. The SOFA (Sepsis-related Organ Failure Assessment) score to describe organ dysfunction/failure. On behalf of the Working Group on Sepsis-Related Problems of the European Society of Intensive Care Medicine.. Intensive Care Med 1996; 22: 707-710.
  • 21 Pencina MJ, D’Agostino RB, Vasan RS. Statistical methods for assessment of added usefulness of new biomarkers. Clin Chem Lab Med 2010; 48: 1703-1711.
  • 22 Simon L, Gauvin F, Amre DK. et al. Serum procalcitonin and C-reactive protein levels as markers of bacterial infection: a systematic review and meta-analysis. Clin Infect Dis 2004; 39: 206-217.
  • 23 West SD, Goldberg D, Ziegler A. et al. Transforming growth factor-beta, macro-phage colony-stimulating factor and C-reactive protein levels correlate with CD14(high)CD16+ monocyte induction and activation in trauma patients. PLoS One 2012; 07: e52406.
  • 24 Tsujioka H, Imanishi T, Ikejima H. et al. Impact of heterogeneity of human peripheral blood monocyte subsets on myocardial salvage in patients with primary acute myocardial infarction. J Am Coll Cardiol 2009; 54: 130-138.
  • 25 Thomas G, Tacke R, Hedrick CC. et al. Nonclassical patrolling monocyte function in the vasculature. Arterioscler Thromb Vasc Biol 2015; 35: 1306-1316.
  • 26 Ingersoll MA, Spanbroek R, Lottaz C. et al. Comparison of gene expression profiles between human and mouse monocyte subsets. Blood 2010; 115: e10-19.
  • 27 Auffray C, Fogg D, Garfa M. et al. Monitoring of blood vessels and tissues by a population of monocytes with patrolling behavior. Science 2007; 317: 666-670.
  • 28 Schauer D, Starlinger P, Reiter C. et al. Intermediate monocytes but not TIE2-expressing monocytes are a sensitive diagnostic indicator for colorectal cancer. PLoS One 2012; 07: e44450.
  • 29 Heine GH, Ortiz A, Massy ZA. et al. Monocyte subpopulations and cardiovascular risk in chronic kidney disease. Nat Rev Nephrol 2012; 08: 362-369.
  • 30 Kwissa M, Nakaya HI, Oluoch H. et al. Distinct TLR adjuvants differentially stimulate systemic and local innate immune responses in nonhuman primates. Blood 2012; 119: 2044-2055.
  • 31 Bajana S, Herrera-Gonzalez N, Narvaez J. et al. Differential CD4(+) T-cell memory responses induced by two subsets of human monocyte-derived dendritic cells. Immunology 2007; 122: 381-393.
  • 32 Tapp LD, Shantsila E, Wrigley BJ. et al. The CD14++CD16+ monocyte subset and monocyte-platelet interactions in patients with ST-elevation myocardial infarction. J Thromb Haemost 2012; 10: 1231-1241.
  • 33 Urra X, Villamor N, Amaro S. et al. Monocyte subtypes predict clinical course and prognosis in human stroke. J Cereb Blood Flow Metab 2009; 29: 994-1002.
  • 34 Wrigley BJ, Shantsila E, Tapp LD. et al. CD14++CD16+ monocytes in patients with acute ischaemic heart failure. Eur J Clin Invest 2013; 43: 121-130.