Early natural killer cell counts in blood predict mortality in severe sepsis.
BACKGROUND
Host immunity should play a principal role in determining both the outcome and recovery of patients with sepsis that originated from a microbial infection. Quantification of the levels of key elements of the immune response could have a prognostic value in this disease.


METHODS
In an attempt to evaluate the quantitative changes in the status of immunocompetence in severe sepsis over time and its potential influence on clinical outcome, we monitored the evolution of immunoglobulins (Igs) (IgG, IgA and IgM), complement factors (C3 and C4) and lymphocyte subsets (CD4+ T cells, CD8+ T cells, B cells (CD19+) and natural killer (NK) cells (CD3-CD16+CD56+)) in the blood of 50 patients with severe sepsis or septic shock at day 1, day 3 and day 10 following admission to the ICU.


RESULTS
Twenty-one patients died, ten of whom died within the 72 hours following admission to the ICU. The most frequent cause of death (n = 12) was multiorgan dysfunction syndrome. At day 1, survivors showed significantly higher levels of IgG and C4 than those who ultimately died. On the contrary, NK cell levels were significantly higher in the patients who died. Survivors exhibited a progressive increase from day 1 to day 10 on most of the immunological parameters evaluated (IgG, IgA, IgM, C3, CD4+, CD8+ T cells and NK cells). Multivariate Cox regression analysis, including age, sex, APACHE II score, severe sepsis or septic shock status and each one of the immunological parameters showed that NK cell counts at day 1 were independently associated with increased risk of death at 28 days (hazard ratio = 3.34, 95% CI = 1.29 to 8.64; P = 0.013). Analysis of survival curves provided evidence that levels of NK cells at day 1 (> 83 cells/mm³) were associated with early mortality.


CONCLUSIONS
Our results demonstrate the prognostic role of NK cells in severe sepsis and provide evidence for a direct association of early counts of these cells in blood with mortality.
Critical Care Medicine Service, Hospital Clínico Universitario-SACYL/ SEMICYUC, Avda Ramón y Cajal 3, E-47005, Valladolid, Spain.
David
D
Andaluz-Ojeda
Verónica
V
Iglesias
Felipe
F
Bobillo
Raquel
R
Almansa
Lucía
L
Rico
Francisco
F
Gandía
Ana Ma
AM
Loma
Concepción
C
Nieto
Rosa
R
Diego
Epifanio
E
Ramos
Mercedes
M
Nocito
Salvador
S
Resino
Jose M
JM
Eiros
Eduardo
E
Tamayo
Raul Ortiz
RO
de Lejarazu
Jesús F
JF
Bermejo-Martin
D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D003176:Complement C3 / Q000032:analysis; D003181:Complement C4 / Q000032:analysis; D005260:Female; D017052:Hospital Mortality; D006801:Humans; D007136:Immunoglobulins / Q000097:blood; D007362:Intensive Care Units / Q000706:statistics & numerical data*; D007694:Killer Cells, Natural / Q000276:immunology*; D018655:Lymphocyte Count; D016131:Lymphocyte Subsets; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D011446:Prospective Studies; D018805:Sepsis / Q000097:blood* / Q000276:immunology / Q000401:mortality*; D013997:Time Factors
D015415:Biomarkers; D003176:Complement C3; D003181:Complement C4; D007136:Immunoglobulins