Minimally invasive surgery induces endotoxin-tolerance in the absence of detectable endotoxemia

Lipopolysaccharide (LPS) tolerance is characterized by an impaired proinflammatory cytokine production upon restimulation of mononuclear cells with LPS. LPS is considered the primary activator for this phenomenon. In response to major injury and extensive abdominal surgery, an immune reaction comparable to LPS tolerance has been described. Therefore, it was investigated whether primary stimuli other than LPS could induce cytokine downregulation. In eight patients who underwent a laparoscopic cholecystectomy, blood was obtained before and after induction of anaesthesia and 2, 6, and 24 hr postoperatively. Ex vivo stimulation of whole blood resulted in a transient reduction (nadir 2 hr postoperatively) of tumor necrosis factor-alpha, interleukin (IL)-1 beta, and interferon-gamma release, while IL-1 receptor antagonist production increased. Stress hormones, LPS-binding protein, and bactericidal/permeability-increasing protein do not seem to be involved. This study shows that minimally invasive surgery, in the absence of endotoxemia, can induce LPS desensitization. These data suggest that prior endotoxemia is not essential for the development of LPS tolerance.