In comparison to those patients who survived, septic patients who died showed lower levels of IgG and C4, along with higher levels of NK cells, in the first 24 hours following admission to the ICU

In comparison to those patients who survived, septic patients who died showed lower levels of IgG and C4, along with higher levels of NK cells, in the first 24 hours following admission to the ICU. 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. == Introduction == Severe sepsis (acute organ dysfunction secondary to infection) and septic shock (severe sepsis plus hypotension not reversed by fluid resuscitation) are major healthcare problems that affect millions of individuals around the world each year, killing one in four (and often more) and increasing in incidence [1-3]. Similarly to polytrauma, acute myocardial infarction and stroke, the early initiation of therapy once severe sepsis is established is likely to influence the patient’s prognosis. In consequence, early identification of individuals at risk for bad outcomes is dramatically important in this condition [4]. Because sepsis originates from a microbial infection, host immunity should play a principal role in determining both outcome and recovery. A protective role of naturally produced immunoglobulin G (IgG) in sepsis was described previously [5]. The participation of cellular immunity in this disease is poorly understood, and the available data are controversial [6-8]. Identifying quantitative alterations in key BM-131246 humoral and cellular parameters could have a prognostic value in this condition. 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 levels of blood of Immunoglobulins (IgG, IgA and IgM), complement factors (C3 and C4), lymphocyte subpopulations (T, B and natural killer (NK) cells) in 50 consecutive patients with a diagnosis of severe sepsis or septic shock at three moments during their hospitalization in the ICU. Our measurement of these parameters provide a first assessment of the status of both humoral Ntn2l and cellular arms of the immune response, and their evaluation is easily available in the vast majority of hospitals with critical care medicine units. == Materials and methods == == Patients == == Inclusion criteria == Patients ages 18 years and older with a diagnosis of severe sepsis or septic shock upon admission to our ICU were prospectively and consecutively recruited from January 2010 to January 2011. The first day following ICU admission was considered day 1 in the analysis. ‘Sepsis’ was defined as suspected infection in the presence of two or more systemic inflammatory response syndrome criteria [9]. ‘Severe sepsis’ was BM-131246 defined as sepsis plus sepsis-induced organ dysfunction or tissue hypoperfusion [10]. Sepsis-induced hypotension was defined as systolic blood pressure (SBP) < 90 mmHg, mean arterial pressure < 70 mmHg or SBP decrease > 40 mmHg or < 2 SD below normal for age in the absence of other causes of hypotension. 'Septic shock' was defined as hypotension (SBP < 90 mmHg) despite adequate fluid resuscitation (> 1,500 ml) or the use of vasoactive agents [10]. Severity BM-131246 of illness was assessed on the basis of two scores: the Acute Physiology and Chronic Health Evaluation II (APACHE II) score for the first 24 hours following diagnosis [11] and the Sequential Organ Failure Assessment (SOFA) score [12]. == Exclusion criteria == Exclusion criteria were the presence of immunodeficiency or concomitant immunosuppressive therapy, pregnancy, do not resuscitate status and cardiac arrest. Approval of the study protocol for both the scientific and ethical aspects was obtained from the Scientific Committee for Clinical Research of our hospital. Informed consent was obtained directly from each patient or his or her legal representative before enrolment. == Microbiological diagnostics == Standard.