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Neslihan Cabioglu, MD, PhD; Sema Bilgic, MSc; Gunnur Deniz, PhD; Esin Aktas, MSc; Yalcn Seyhun, MD; Akif Turna, MD; Kayhan Gunay, MD; Figen Esen, MD

Arch Surg. 2002;137:1037-1043.

Background  High levels of tumor necrosis factor (TNF) 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-, TNF-, 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- 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- and monocyte-associated IL-10 and TNF- 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.

From the Departments of Surgery (Drs Cabioglu and Gunay), Medical Biology (Dr Seyhun), and Anesthesiology (Dr Esen), Istanbul Faculty of Medicine, and the Division of Immunology, Institute of Experimental and Medical Research (Drs Cabioglu, Deniz, and Turna and Mss Bilgic and Aktas), University of Istanbul, Istanbul, Turkey. Dr Cabioglu is now with the Departments of Cancer Biology and Surgical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston.

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