Decreased Cytokine Expression in Peripheral Blood Leukocytes of Patients With Severe Sepsis

BACKGROUND: High levels of tumor necrosis factor (TNF) alpha messenger RNAs and interleukin (IL) 8 have been reported in leukocytes of patients with sepsis. HYPOTHESIS: Assessment of leukocyte intracytoplasmic levels of proinflammatory and anti-inflammatory cytokines might be clinically more relevant to determine prognosis in patients with severe sepsis. DESIGN: Cohort study. SETTING: Surgical intensive care units of a university hospital. PATIENTS AND INTERVENTIONS: Leukocyte suspensions obtained from 16 patients, 6 during early sepsis or septic shock and 10 during late sepsis or septic shock, were incubated with anti-CD14 and anti-CD2 or anti-CD3 monoclonal antibodies and then with intracytoplasmic anticytokine antibodies staining for interferon-gamma, TNF-alpha, IL-2, IL-6, IL-8, IL-10, and IL-12 and analyzed with a flow cytometer. MAIN OUTCOME MEASURES: Mann-Whitney test and Spearman correlation test were used in statistical evaluations according to the 28-day all-cause mortality rates and multiple organ dysfunction and sepsis-related organ failure assessment scores. RESULTS: Higher serum IL-6, IL-8, C-reactive protein, and procalcitonin levels were found in patients with high multiple organ dysfunction and sepsis-related organ failure assessment scores (greater than or equal to the median values [8 and 11, respectively]), in contrast to decreased T-lymphocyte-associated IL-6 and TNF-alpha and monocyte-associated IL-10 and IL-12 proportions. Furthermore, in 28-day all-cause mortality analysis, there were higher levels of C-reactive protein and procalcitonin in nonsurvivors (n = 9) than in survivors (n = 7), while T-lymphocyte-associated IL-2, IL-6, IL-10, and TNF-alpha and monocyte-associated IL-10 and TNF-alpha proportions decreased in the nonsurvivors. CONCLUSION: These results suggest that diminished lymphocyte- and monocyte-associated proinflammatory and anti-inflammatory cytokine levels are associated with worse prognosis in patients with severe sepsis.