Endotoxin, TNF-alpha, Interleukin-6 and Parameters of the Cellular Immune System in Patients with Intraabdominal Sepsis

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Abstract
The correlation of endotoxin (ET), tumor necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6), and cellular immune parameters with multiple organ failure and lethal outcome in intraabdominal infections was studied in a group of 18 patients with peritonitis, abscess or pancreatitis. Of these patients, 7 developed respiratory failure and 5 died due to multiple septic organ failure. The peak levels of ET (2.7 ± 1.3 ng/ml) in the course of the disease were followed by moderate increases of TNF-alpha (mean 147 ± 41 pg/ml) and IL-6 (170 ± 61 pg/ml) within 2 days. Analysis of the parameters for the last 12 days prior to death or discharge showed, that the patient group with lethal outcome was characterized by significant lower mean plasma levels of TNF-alpha (< 75 pg/ml versus > 160 pg/ml) and IL-6 (< 130 pg/ml versus > 270 pg/ml), as well as high rates of unstimulated thymidine uptake into peripheral mononuclear blood cells (> 44000 cpm/8 × 106 PMBC/18 h versus < 24000 cmp), T-lymphocyte depression (CD3; approximately > 40% reduction) with lower T-helper/inducer subset cell numbers (mean CD4:CD8 ratio 1.0 ± 0.55 versus 1.8 ± 0.2) and lower lectin (PHA) stimulation values (1.9 ± 1.4 versus 4.1 ± 1.0). These data demonstrate an anergic immune status with low mediator levels and depressed T-lymphocyte function in patients with poor prognosis. Therefore the therapeutic modalities should consist of immunorestorative measures and all attempts to neutralize mediators as TNF-alpha and IL-6 are likely to have further adverse effects on the immune system in the late stages of intraabdominal infections.