Monocytic Deactivation and Production of Tumour Necrosis Factor-α ex vivo: Prognostic Parametersin Patients of ICU

Overview

Objective:
Dysbalance in immune system play an important role in pathogenesis of sepsis and systemic inflammatoryresponse syndrome (SIRS). Lowered expression of HLA-DR on monocytes coupled with decreased production of tumornecrosis factor-α ex vivo after stimulation with lipopolysaccharide are characteristic features of immunoparalysis.Thestudyaimed to determine importance and feasibility of their evaluation in patients with SIRS, sepsis and septic shock.Design: Retrospective, cohort study.Setting: Multidisciplinary intensive care unit.Material and methods: 67 patients meeting the criteria for diagnosis of systemic inflammatory response syndrome (SIRS),sepsis and septic shock according to the Consens Conference in 1991, admitted to the intensive care units were examined.For determination of HLA-DR expression on monocytes flow cytometry was used and production of TNF-α ex vivo fromwhole blood after lipopolysaccharide stimulation was evaluated by chemiluminiscence method utilising VollblutstimulationKit (Millenia).Results: Expression of HLA-DR on monocytes and TNF-α production were significantly decreased in patients with SIRS,sepsis and septic shock compared to the control group (P < 0.001) and correlated significantly with diagnosis (Spearman´scorrelation coefficient r = -0.38, resp. r = -0.40, P < 0.0001). We found significant differences of both parameters betweensubgroups of patients with SIRS and sepsis or SIRS and septic shock.The values of expression of HLA-DR correlated significantly with values of TNF-α in patients with SIRS and sepsis (P =0.0004, resp. P = 0.0003).Last measured values of HLA-DR expression on monocytes and production of TNF-α were significantly lower in non-survivalscompared to survived (P < 0.001, resp. P < 0.05).Conclusion:HLA-DR expression on monocytes and production of TNF-α ex vivo decrease in early phase of SIRS and sepsis.Long lasting duration of their lower values is associated with unfavourable clinical outcome.

Key words:
HLA-DR – monocytes – immunoparalysis – sepsis – systemic inflammatory response syndrome – tumournecrosis factor-α