Top

Published in:

01-12-2003 | Experimental

Human leukocyte antigen-DR expression in peripheral blood mononuclear cells from healthy donors influenced by the sera of injured patients prone to severe sepsis

Authors: Anke Mueller, Ernst Kreuzfelder, Baerbel Nyadu, Monika Lindemann, Vera Rebmannn, Matthias Majetschak, Udo Obertacke, Ulrich F. Schade, Dieter Nast-Kolb, Hans Grosse-Wilde

Published in: Intensive Care Medicine | Issue 12/2003

Abstract

Objective

To study the influence of sera from severely injured patients on the human leukocyte antigen (HLA)-DR expression of normal peripheral blood mononuclear cells (PBMC).

Design

In vitro study.

Setting

University hospital.

Patients and participants

Sera from 34 patients were obtained within 8 h after trauma. Seventeen of these patients developed posttraumatic sepsis (sepsis group) and 17 recovered without infectious complications. Sera from ten healthy individuals served as controls. Phytohemagglutinin (PHA)-activated PBMC from 44 healthy donors were used to study the effects of a patient's serum.

Measurements and results

Medium containing 5% of serum from the sepsis group significantly (p<0.05) reduced the HLA-DR expression (channels, mean ± standard error of the mean) on monocytes (patients 883±22, controls 962±15), B (patients 922±14, controls 972±7) and T cells (patients 932±13, controls 968±5) of PHA-activated PBMC. Significantly increased accumulation of TNFα on (1.8±0.4% of PBMC) and within T cells (0.98±0.26% of PBMC) was observed by flow cytometry after incubation with medium containing sera of the sepsis group compared with controls (on 0.5±0.1%, within 0.27±0.05% of PBMC). A significant negative correlation between relative cell counts of intracellular TNFα-positive T cells with HLA-DR expression was observed for monocytes (r= −0.61), B cells (r= −0.57) and proliferation (r= −0.68) as estimated by ³H-thymidine uptake [patients 139,971±12,844 counts per minute (cpm), controls 198,973±19,347 cpm, p<0.05] in the presence of sera from the sepsis group.

Conclusions

Reduced cellular immunity and, therefore, immunodeficiency after trauma appears to be caused by soluble factors influencing T cell function in particular.

Mach B, Steimle V, Martinez-Soria E, Reith W (1994) Regulation of MHC class II genes: lessons from a disease. Annu Rev Immunol 14:301–331CrossRef

Botazzo GF, Pujol-Borrell R, Hanafusa T, Feldmann M (1983) Role of aberrant HLA-DR expression and antigen presentation in induction of endocrine autoimmunity. Lancet 2:1115–1119CrossRef

Goris RJA, Draaisma J (1982) Causes of death after blunt trauma. J Trauma 22:141–146CrossRef

Centers for Disease Control (1990) Increase in national hospital discharge survey rates for septicemia—United States, 1979–1987. JAMA 263:937–938CrossRef

Cheadle WG, Hershman MJ, Wellhausen SR, Davidson PF, Polk HC Jr (1991) HLA-DR antigen expression on peripheral blood monocytes correlates with surgical infection. Am J Surg 161:639–645CrossRef

Wakefield CH, Carey PD, Foulds S, Monson JRT, Guillou PJ (1993) Changes in major histocompatibility complex II expression in monocytes and T cells of patients developing infection after surgery. Br J Surg 80:205–209CrossRef

Ditschkowski M, Kreuzfelder E, Majetschak M, Obertacke U, Schade FU, Grosse-Wilde H (1999) Reduced B cell HLA-DR expression and natural killer cell counts in patients prone to sepsis after injury. Eur J Surg 165:1129–1133CrossRef

Ditschkowski M, Kreuzfelder E, Rebmann V, Ferencik S, Majetschak M, Schmid E, Obertacke U, Hirche H, Schade FU, Grosse-Wilde H (1999) HLA-DR expression and soluble HLA-DR levels in septic patients after trauma. Ann Surg 299:246–254CrossRef

Majetschak M, Flach R, Heukamp T, Jennissen V, Obertacke U, Neudeck F, Schmit-Neuerburg KP, Schade FU (1997) Regulation of whole blood tumor necrosis factor production upon endotoxin stimulation after severe blunt trauma. J Trauma 43:880–887CrossRef

10.

Majetschak M, Börgermann J, Waydhas C, Obertacke U, Nast-Kolb D, Schade FU (2000) Whole blood tumor necrosis-alpha production and its relation to systemic concentrations of interleukin 4, interleukin 10 and transforming growth factor-beta1 in multiply injured blunt trauma patients. Crit Care Med 28:1847–1853CrossRef

11.

Baker SP, O´Neill B, Haddon W, Long WB (1974) The injury severity score: a method for describing patients with multiple injuries and evaluating emergency care. J Trauma 14:187–196CrossRef

12.

American College of Chest Physicians/Society of Critical Care Medicine consensus conference (1992) Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Crit Care Med 20:864–874CrossRef

13.

Maschke J, Menne S, Jacob JR, Kreuzfelder E, Tennant BC, Roggendorf M, Grosse-Wilde H (2001) Thymidine utilization abnormality in proliferating lymphocytes and hepatocytes of the woodchuck. Vet Immunol Immunopathol 78:279–296CrossRef

14.

Fumeaux T, Pugin J (2002) Role of interleukin-10 in the intracellular sequestration of human leukocyte antigen-DR in monocytes during septic shock. Am J Respir Crit Care Med 166:1475–1489CrossRef

15.

Bone RC (1996) Sir Issaac Newton, sepsis, SIRS and CARS. Crit Care Med 24:1125–1128CrossRef

16.

Munford RS, Pugin J (2001) Normal responses to injury prevent systemic inflammation and can be immunosuppressive. Am J Respir Crit Care Med 163:316–321CrossRef

17.

Benoist C, Mathis D (1990) Regulation of major histocompatibility complex class II genes: X, Y and other letters of the alphabet. Annu Rev Immunol 8:681–715CrossRef

18.

Glimcher LH, Kara CJ (1992) Sequences and factors: a guide to MHC class II transcription. Annu Rev Immunol 10:13–49CrossRef

19.

Dufour C, Corcione A, Svahn J, Haupt R, Battilana N, Pistoia V (2001) Interferon γ and tumour necrosis factor α are overexpressed in bone marrow T lymphocytes from paediatric patients with aplastic anaemia. Br J Haematol 115:1023–1031CrossRef

20.

Bo X, Broome U, Remberger M, Sumitran-Holgersson S (2001) Tumour necrosis factor alpha impairs function of liver derived lymphocytes and natural killer cells in patients with primary sclerosing cholangitis. Gut 49:131–141CrossRef

21.

Takahashi K, Takigawa M, Arai H, Kurihara H, Murayama Y (1994) The inhibition of interferon-gamma-induced upregulation of HLA-DR expression on cultured human gingival fibroblasts by interleukin-1 beta or tumor necrosis factor-alpha. J Peridontol 65:336–341CrossRef

22.

Konig, A, Happle, R, Hoffmann, R (1997) IFN-gamma-induced HLA-DR but not ICAM-1 expression on cultured dermal papilla cells is downregulated by TNF-alpha. Arch Dermatol Res 289:466–470CrossRef

23.

Watanabe Y, Jacob CO (1991) Regulation of MHC class II antigen expression. Opposing effects of tumor necrosis factor-alpha on IFN-gamma-induced HLA-DR and Ia expression depends on the maturation and differentiation stage of the cell. J Immunol 146:899–905PubMed

24.

Yoshimoto, T, Takeda, K, Tanaka, Z, Ohkusu, K, Kashiwamura, S, Okamura, H, Akira, S, Nakanishi, K (1998) IL-12 up-regulates IL-18 receptor expression on T cells, TH 1 cells and B cells: synergism with IL-18 for IFN γ production. J Immunol 161:3400–3407

25.

Davis, GS, Pfeiffer, LM, Hemenway, DR (2000) Interferon-γ production by specific lung lymphocyte phenotypes in silicosis in mice. Am J Respir Cell Mol Biol 22:491–501CrossRef

26.

Dustin ML (2002) Membrane domains and the immunological synapse: keeping T cells resting and ready. J Clin Invest 109:155–160CrossRef

Title: Human leukocyte antigen-DR expression in peripheral blood mononuclear cells from healthy donors influenced by the sera of injured patients prone to severe sepsis
Authors: Anke Mueller
Ernst Kreuzfelder
Baerbel Nyadu
Monika Lindemann
Vera Rebmannn
Matthias Majetschak
Udo Obertacke
Ulrich F. Schade
Dieter Nast-Kolb
Hans Grosse-Wilde
Publication date: 01-12-2003
Publisher: Springer Berlin Heidelberg
Published in: Intensive Care Medicine / Issue 12/2003
Print ISSN: 0342-4642
Electronic ISSN: 1432-1238
DOI: https://doi.org/10.1007/s00134-003-1992-8

At a glance: The STEP trials

Springer Medicine

Human leukocyte antigen-DR expression in peripheral blood mononuclear cells from healthy donors influenced by the sera of injured patients prone to severe sepsis

Abstract

Objective

Design

Setting

Patients and participants

Measurements and results

Conclusions

At a glance: The STEP trials

Springer Medicine

Abstract

Objective

Design

Setting

Patients and participants

Measurements and results

Conclusions

Please log in to get access to this content

Other articles of this Issue 12/2003

Erratum to: Comparison of effectiveness of two urinary drainage systems in intensive care unit: a prospective, randomized clinical trial

Elevated troponin T concentrations in critically ill patients

Prone ventilation following witnessed pulmonary aspiration: the effect on oxygenation

Searching for evidence: don’t forget the foundations

Do different mattresses affect the quality of cardiopulmonary resuscitation?

Alcohol withdrawal severity is decreased by symptom-orientated adjusted bolus therapy in the ICU