Scientific Papers
Selective defects of T lymphocyte function in patients with lethal intraabdominal infection

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Abstract

Background: In recent models, compensatory antiinflammatory immune reactions triggered in response to systemic inflammation were considered important for the outcome of sepsis. The present study investigated T-cell functions in patients with postoperative sepsis due to intra-abdominal infection.

Methods: Peripheral T cells were purified from 32 sepsis patients and 41 healthy controls. Proliferation and production of interferon (IFN)-γ, interleukin (IL)-2, IL-4, tumor necrosis factor (TNF), and IL-10 were stimulated by cross-linking of CD3 and CD28.

Results: T-cell proliferation and production of IL-2 and TNF were severely suppressed in patients with lethal intraabdominal infection as compared with survivors and healthy controls. Sepsis survivors showed normal T-cell proliferation and IL-2 release, whereas secretion of TNF was reduced. However, TNF suppression in survivors was less severe than in nonsurviving patients. Defective T-cell functions were observed at the onset of sepsis and persisted throughout the entire observation period. T-cell production of IL-4 and IL-10 was not affected by postoperative intraabdominal infection.

Conclusions: Defective T-cell proliferation and secretion of IL-2 and TNF correlate with sepsis mortality, thus indicating an important role of T cells for the immune defense against postoperative infection. Immune defects were evident at the onset of sepsis, suggesting that immunosuppression may develop as a primary response to sepsis without preceding immune hyperactivity.

Section snippets

Patient population and study design

Thirty-two consecutive sepsis patients treated in the surgical intensive care unit were included in the study. Sepsis was caused by intraabdominal infection following major surgery in all patients. The clinical profiles of the patients enrolled in the study are detailed in the Table. Patients with acquired or inherited immunodeficiencies and patients receiving immunosuppressive therapy were excluded from the study. Beginning at the day of diagnosis of sepsis, venous blood samples were collected

Results

T-cell functions were investigated in 32 consecutive patients who developed sepsis as a result of postoperative intraabdominal infection. The clinical profile of these patients is detailed in the Table. The overall mortality of sepsis was 40.6% (13 of 32 patients). To analyze whether alterations in T-cell functions may correlate with the course or outcome of intraabdominal infection, cell proliferation and cytokine release were determined during the onset and final course of sepsis as defined

Comments

Although sepsis was shown to result in immune hyperactivity, it may also be associated with severe immune defects, many of which have been observed in circulating monocytes. For example, downregulated production of proinflammatory cytokines including TNF, IL-1, and IL-6 has been described in sepsis patients using endotoxin-stimulated whole blood or isolated adherent cells.16, 17, 18 The present study, however, focused on the role of T lymphocytes for intraabdominal infection-induced

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    This work was supported by Grants Si 208/5-1 and Si 208/5-4 from the Deutsche Forschungsgemeinschaft to the clinical research group “Immunsuppression und postoperative Sepsis.”

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