Sepsis-induced long-term immune paralysis - results of a descriptive, explorative study

被引:84
作者
Arens, C. [1 ]
Bajwa, S. A. [2 ]
Koch, C. [2 ]
Siegler, B. H. [1 ]
Schneck, E. [2 ]
Hecker, A. [3 ]
Weiterer, S. [1 ]
Lichtenstern, C. [1 ]
Weigand, M. A. [1 ]
Uhle, F. [1 ]
机构
[1] Heidelberg Univ Hosp, Dept Anesthesiol, Neuenheimer Feld 110, D-69120 Heidelberg, Germany
[2] Univ Hosp Giessen & Marburg, Dept Anesthesiol & Intens Care Med, Giessen, Germany
[3] Univ Hosp Giessen & Marburg, Dept Gen & Thorac Surg, Giessen, Germany
关键词
Sepsis; Immunology; Immune system; Immunocompromised; HLA-DR EXPRESSION; IMMUNOSUPPRESSION; INFLAMMATION; INFECTION; SUSCEPTIBILITY; PATHOGENESIS; MORTALITY;
D O I
10.1186/s13054-016-1233-5
中图分类号
R4 [临床医学];
学科分类号
1002 ; 100602 ;
摘要
Background: Long-lasting impairment of the immune system is believed to be the underlying reason for delayed deaths after surviving sepsis. We tested the hypothesis of persisting changes to the immune system in survivors of sepsis for the first time. Methods: In our prospective, cross-sectional pilot study, eight former patients who survived catecholamine-dependent sepsis and eight control individuals matched for age, sex, diabetes and renal insufficiency were enrolled. Each participant completed a questionnaire concerning morbidities, medications and infection history. Peripheral blood was collected for determination of i) immune cell subsets (CD4(+), CD8(+) T cells; CD25(+) CD127(-) regulatory T cells; CD14(+) monocytes), ii) cell surface receptor expression (PD-1, BTLA, TLR2, TLR4, TLR5, Dectin-1, PD-1 L), iii) HLA-DR expression, and iv) cytokine secretion (IL-6, IL10, TNF-alpha, IFN-gamma) of whole blood stimulated with either a-CD3/28, LPS or zymosan. Results: After surviving sepsis, former patients presented with increased numbers of clinical apparent infections, including those typically associated with an impaired immune system. Standard inflammatory markers indicated a low-level inflammatory situation in former sepsis patients. CD8(+) cell surface receptor as well as monocytic HLA-DR density measurements showed no major differences between the groups, while CD4(+) T cells tended towards two opposed mechanisms of negative immune cell regulation via PD-1 and BTLA. Moreover, the post-sepsis group showed alterations in monocyte surface expression of distinct pattern recognition receptors; most pronouncedly seen in a decrease of TLR5 expression. Cytokine secretion in response to important activators of both the innate (LPS, zymosan) and the adaptive immune system (a-CD3/ 28) seemed to be weakened in former septic patients. Conclusions: Cytokine secretion as a reaction to different activators of the immune system seemed to be comprehensively impaired in survivors of sepsis. Among others, this could be based on trends in the downregulation of distinct cell surface receptors. Based on our results, the conduct of larger validation studies seems feasible, aiming to characterize alterations and to find potential therapeutic targets to engage.
引用
收藏
页数:11
相关论文
共 39 条
  • [1] Does prior sepsis alter subsequent circadian and sickness behaviour response to lipopolysaccharide treatment in mice?
    Anderson, Sean T.
    O'Callaghan, Emma K.
    Commins, Sean
    Coogan, Andrew N.
    [J]. JOURNAL OF NEURAL TRANSMISSION, 2015, 122 : 63 - 73
  • [2] Lipopolysaccharide-induced sepsis induces long-lasting affective changes in the mouse
    Anderson, Sean T.
    Commins, Sean
    Moynagh, Paul N.
    Coogan, Andrew N.
    [J]. BRAIN BEHAVIOR AND IMMUNITY, 2015, 43 : 98 - 109
  • [3] [Anonymous], CRIT CARE MED
  • [4] Septic mice are susceptible to pulmonary aspergillosis
    Benjamim, CF
    Hogaboam, CM
    Lukacs, NW
    Kunkel, SL
    [J]. AMERICAN JOURNAL OF PATHOLOGY, 2003, 163 (06) : 2605 - 2617
  • [5] Sepsis: A new hypothesis for pathogenesis of the disease process
    Bone, RC
    Grodzin, CJ
    Balk, RA
    [J]. CHEST, 1997, 112 (01) : 235 - 243
  • [6] DEFINITIONS FOR SEPSIS AND ORGAN FAILURE AND GUIDELINES FOR THE USE OF INNOVATIVE THERAPIES IN SEPSIS
    BONE, RC
    BALK, RA
    CERRA, FB
    DELLINGER, RP
    FEIN, AM
    KNAUS, WA
    SCHEIN, RMH
    SIBBALD, WJ
    [J]. CHEST, 1992, 101 (06) : 1644 - 1655
  • [8] Boomer JS, 2014, VIRULENCE, V5, P45, DOI [10.4161/viru.27794, 10.4161/viru.26516]
  • [9] A prospective analysis of lymphocyte phenotype and function over the course of acute sepsis
    Boomer, Jonathan S.
    Shuherk-Shaffer, Jennifer
    Hotchkiss, Richard S.
    Green, Jonathan M.
    [J]. CRITICAL CARE, 2012, 16 (03):
  • [10] Immunosuppression in Patients Who Die of Sepsis and Multiple Organ Failure
    Boomer, Jonathan S.
    To, Kathleen
    Chang, Kathy C.
    Takasu, Osamu
    Osborne, Dale F.
    Walton, Andrew H.
    Bricker, Traci L.
    Jarman, Stephen D., II
    Kreisel, Daniel
    Krupnick, Alexander S.
    Srivastava, Anil
    Swanson, Paul E.
    Green, Jonathan M.
    Hotchkiss, Richard S.
    [J]. JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2011, 306 (23): : 2594 - 2605