Alterations in function and phenotype of monocytes from patients with septic disease--predictive value and new therapeutic strategies

Abstract

Recently we described the predictive value of the proportion of HLA-DR+ peripheral blood monocytes for the clinical outcome of septic disease in immunosuppressed patients (allograft recipients) and surgical patients mostly with peritonitis as septic focus (following perforation of gastrointestinal tract). The experiments described here show that the loss of HLA-class II antigen expression and other phenotypical abnormalities of monocytes from septic patients with fatal outcome are associated with functional defects (antigen presentation, formation of reactive oxygen species, cytokine secretion). The picture of phenotypical and functional defects of monocytes was termed "immunoparalysis" (leading parameter: loss of HLA-DR antigen expression less than 20%). Interferon-gamma as well as GM-CSF normalized in vitro the surface antigen expression on monocytes derived from septic patients with "immunoparalysis". However, sera from patients with "immunoparalysis" prevented the cytokine-mediated effects on HLA-DR antigen expression. The inhibitory activity in septic sera was not dialysable. In order to remove such factors we started a plasmapheresis study in septic patients selected for "immunoparalysis". The preliminary data of this clinical trial suggest an improved survival rate.