Comparison of monocyte functions after LPS-or IL-10 induced reorientation:Importance in clinical immunoparalysis

Immunoparalysis is an acquired immunodeficiency which may occur in patients after major surgery, burns, polytrauma and sepsis. It is associated with a modified state of monocytes marked by their altered capacity to induce ant igen-specific T cell stimulation and to release various cytokines. However, the pathogenesis of immunoparalysis may differ in various patient groups. It can develop in patients after systemic hyperinflammation induced by gast rointestinal translocation of endotoxin (lipopolysaccharide, LPS) or sepsis , as well as in patients without preceding systemic inflammation but primar y anti-inflammation, for instance induced by sympathetic activation. To fur ther elucidate the syndrome, we compared endotoxin tolerance as a model of immunoparalysis after systemic hyperinflammation versus interleukin-10 (IL- 10) treatment as a model of primarily anti-inflammation-induced immunoparal ysis. In vitro priming of peripheral blood mononuclear cells with either LP S or IL-10 for 24 h led to a strongly or moderately diminished LPS-induced tumor necrosis factor-alpha (TNF-alpha) production, compared to unprimed co ntrols, respectively. Furthermore, LPS-induced reduction of TNF-alpha produ ction capacity persisted over the following days whereas IL-10-primed monoc ytes rapidly recovered. Similarly, in contrast to persistently diminished M HC class II expression in LPS-treated monocytes, IL-10 only transiently dow nregulated these molecules. Consequently, in contrast to IL-10-primed monoc ytes, LPS-primed monocytes were greatly impaired in their capacity to induc e antigen-specific T cell proliferation and IFN-gamma production. These dat a indicate that LPS priming provokes a more profound modulation of monocyte function than IL-10 priming, raising the question of possible variations i n the clinical course of immunoparalysis, dependent on its pathogenesis. Co pyright (C) 2000 S. Karger AG, Basel.