Dataset Information

Phenotype and functions of natural killer cells in critically-ill septic patients.

ABSTRACT:

Rationale

Natural killer cells, as a major source of interferon-?, contribute to the amplification of the inflammatory response as well as to mortality during severe sepsis in animal models.

Objective

We studied the phenotype and functions of circulating NK cells in critically-ill septic patients.

Methods

Blood samples were taken <48 hours after admission from 42 ICU patients with severe sepsis (n?=?15) or septic shock (n?=?14) (Sepsis group), non-septic SIRS (n?=?13) (SIRS group), as well as 21 healthy controls. The immuno-phenotype and functions of NK cells were studied by flow cytometry.

Results

The absolute number of peripheral blood CD3-CD56(+) NK cells was similarly reduced in all groups of ICU patients, but with a normal percentage of NK cells. When NK cell cytotoxicity was evaluated with degranulation assays (CD107 expression), no difference was observed between Sepsis patients and healthy controls. Under antibody-dependent cell cytotoxicity (ADCC) conditions, SIRS patients exhibited increased CD107 surface expression on NK cells (62.9[61.3-70]%) compared to healthy controls (43.5[32.1-53.1]%) or Sepsis patients (49.2[37.3-62.9]%) (p?=?0.002). Compared to healthy (10.2[6.3-13.1]%), reduced interferon-? production by NK cells (K562 stimulation) was observed in Sepsis group (6.2[2.2-9.9]%, p<0.01), and especially in patients with septic shock. Conversely, SIRS patients exhibited increased interferon-? production (42.9[30.1-54.7]%) compared to Sepsis patients (18.4[11.7-35.7]%, p<0.01) or healthy controls (26.8[19.3-44.9]%, p?=?0.09) in ADCC condition.

Conclusions

Extensive monitoring of the NK-cell phenotype and function in critically-ill septic patients revealed early decreased NK-cell function with impaired interferon-? production. These results may aid future NK-based immuno-interventions.

Trial registration

NTC00699868.

SUBMITTER: Forel JM

PROVIDER: S-EPMC3516510 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Publications

Phenotype and functions of natural killer cells in critically-ill septic patients.

Forel Jean-Marie JM Chiche Laurent L Thomas Guillemette G Mancini Julien J Farnarier Catherine C Cognet Céline C Guervilly Christophe C Daumas Aurélie A Vély Frédéric F Xéridat François F Vivier Eric E Papazian Laurent L

PloS one 20121206 12

<h4>Rationale</h4>Natural killer cells, as a major source of interferon-γ, contribute to the amplification of the inflammatory response as well as to mortality during severe sepsis in animal models.<h4>Objective</h4>We studied the phenotype and functions of circulating NK cells in critically-ill septic patients.<h4>Methods</h4>Blood samples were taken <48 hours after admission from 42 ICU patients with severe sepsis (n = 15) or septic shock (n = 14) (Sepsis group), non-septic SIRS (n = 13) (SIRS ...[more]

PMID: 23236375

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Project description:BACKGROUND:Associations among inflammatory cytokines, erythropoietin (EPO), and anemia in critically ill septic patients remain unclear. This study tested the hypothesis that elevated inflammatory cytokines and decreased EPO would be associated with iron-restricted anemia while accounting for operative blood loss, phlebotomy blood loss, and red blood cell (RBC) transfusion volume. METHODS:Prospective observational cohort study of 42 critically ill septic patients was conducted. Hemoglobin (Hb) at sepsis onset and hospital discharge were used to calculate ?Hb. Operative blood loss, phlebotomy blood loss, and RBC transfusion volume were used to calculate adjusted ?Hb (Adj?Hb) assuming that 300 mL RBC is equal to 1 g/dL Hb. Patients with Adj?Hb of greater than 0 (positive Adj?Hb, n = 18) were compared with patients with Adj?Hb of less than or equal to 0 (negative Adj?Hb, n = 24). RESULTS:Plasma tumor necrosis factor ?, granulocyte colony-stimulating factor, interleukin (IL)-6, IL-8, EPO, erythrocyte mean corpuscular volume, and serum transferrin receptor were measured on days 0, 1, 4, 7, and 14. Patients with negative Adj?Hb had significantly higher day 14 levels of IL-6 (37.4 vs. 15.2 pg/mL, p < 0.05), IL-8 (39.1 vs. 18.2 pg/mL, p = 0.01), and granulocyte colony-stimulating factor (101.3 vs. 60.5 pg/mL, p = 0.01), but not EPO. On linear regression analysis, lower Adj?Hb was associated with higher day 14 levels of IL-6 (r = 0.22, p < 0.01), IL-8 (r = 0.10, p = 0.04), stromal cell-derived factor 1 (r = 0.14, p = 0.02), and tumor necrosis factor ? (r = 0.13, p = 0.02), but not EPO. Patients with negative Adj?Hb had significantly lower mean corpuscular volume on days 4 (89.6 vs. 93.2 fL/cell, p = 0.04), 7 (92.3 vs. 94.9 fL/cell, p = 0.04), and 14 (92.1 vs. 96.0 fL/cell, p = 0.03) but similar serum transferrin receptor levels. CONCLUSION:Persistent elevation of inflammatory cytokines was associated with iron-restricted anemia among critically ill septic patients, occurring in the absence of systemic iron deficiency, independent of endogenous EPO. LEVEL OF EVIDENCE:Prognostic study, level II.

Dataset Information

Phenotype and functions of natural killer cells in critically-ill septic patients.

Rationale

Objective

Methods

Results

Conclusions

Trial registration

Publications

Phenotype and functions of natural killer cells in critically-ill septic patients.

Similar Datasets

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