title: Immunoparalysis: Clinical and immunological associations in SIRS and severe sepsis patients.
abstract: This study was designed to identify changes in the monocytic membrane marker HLA-DR and heat shock proteins (HSPs) in relation to T-regulatory cells (T-regs) and other immunological marker changes in patients with systemic inflammatory response syndrome (SIRS) or sepsis/septic shock.
  
  
  
  Healthy volunteers, intensive care unit (ICU) patients with SIRS due to head injury and ICU patients with severe sepsis/septic shock were enrolled in the current study. Determination of CD14+/HLA-DR+ cells, intracellular heat-shock proteins and other immunological parameters were performed by flow cytometry and RT-PCR techniques as appropriate. Univariate and multivariate analysis examined associations of CD14/HLA-DR, HSPs, T-regs and suppressor of cytokine signalling (SOCS) proteins with SIRS, sepsis and outcome.
  
  
  
  Fifty patients (37 with severe sepsis and 13 with SIRS) were enrolled, together with 20 healthy volunteers used as a control group. Compared to healthy individuals, patients with SIRS and severe sepsis showed progressive decline of their CD14/HLA-DR expression (0% to 7.7% to 50% within each study subpopulation, p<0.001). Mean fluorescent intensity (MFI) levels of HSP70 and HSP90 on monocytes and polymorphonuclear cells were significantly higher in SIRS patients compared to controls and fell significantly in severe sepsis/septic shock patients (p<0.05 for all comparisons). There was no statistically significant difference between subgroups for levels of T-regulatory cells or relative copies of Suppressor of Cytokine Signalling 3 (SOCS3) proteins. In univariate models percent of CD14/HLA-DR was associated with mortality (OR: 1.8 95%CI 1.02-3.2, p=0.05), while in multivariate models after adjusting for CD14/HLA-DR only younger age and lower Acute Physiology and Chronic Health Evaluation II (APACHE II) scores were associated with increased chances of survival (beta -0.05, OR 0.9, 95% CI 0.9-0.99, p=0.038 for age and beta -0.11, OR 0.89, 95% CI 0.8-0.99, p=0.037 for APACHE II score).
  
  
  
  Significant associations with SIRS and sepsis were found for CD14/HLA-DR expression and monocyte and polymorphonuclear cell levels of HSP70 and 90. The role of these biomarkers in assessing the prognosis of sepsis needs to be further explored and validated in prospective studies.
authors.affiliation: 2nd Department of Critical Care, Attikon University Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Papadopoulos
authors.affiliation: 4th Department of Internal Medicine, Attikon University Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: Aikaterini
authors.initials: A
authors.lastname: Pistiki
authors.affiliation: 2nd Department of Critical Care, Attikon University Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: Maria
authors.initials: M
authors.lastname: Theodorakopoulou
authors.affiliation: 2nd Department of Critical Care, Attikon University Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: Theodora
authors.initials: T
authors.lastname: Christodoulopoulou
authors.affiliation: 4th Department of Internal Medicine, Attikon University Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: Georgia
authors.initials: G
authors.lastname: Damoraki
authors.affiliation: First Department of Propaedeutic Internal Medicine, Laikon University Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: Dimitris
authors.initials: D
authors.lastname: Goukos
authors.affiliation: First Department of Propaedeutic Internal Medicine, Laikon University Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: Efrossini
authors.initials: E
authors.lastname: Briassouli
authors.affiliation: 2nd Department of Critical Care, Attikon University Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: Ioanna
authors.initials: I
authors.lastname: Dimopoulou
authors.affiliation: 2nd Department of Critical Care, Attikon University Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: Apostolos
authors.initials: A
authors.lastname: Armaganidis
authors.affiliation: First Critical Care Department, Evangelismos Hospital, University of Athens, Athens, Greece.
authors.forename: Serafim
authors.initials: S
authors.lastname: Nanas
authors.affiliation: Pediatric Intensive Care Unit, University Hospital, University of Crete, Heraklion, Greece.
authors.forename: George
authors.initials: G
authors.lastname: Briassoulis
authors.affiliation: 4th Department of Internal Medicine, Attikon University Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece. Electronic address: Sotirios.tsiodras@gmail.com.
authors.forename: Sotirios
authors.initials: S
authors.lastname: Tsiodras
mesh_terms: D000368:Aged; D018572:Disease-Free Survival; D005260:Female; D006684:HLA-DR Antigens / Q000276:immunology*; D018840:HSP70 Heat-Shock Proteins / Q000276:immunology; D018841:HSP90 Heat-Shock Proteins / Q000276:immunology; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology* / Q000473:pathology; D012772:Shock, Septic / Q000276:immunology* / Q000401:mortality* / Q000473:pathology; D000071223:Suppressor of Cytokine Signaling 3 Protein / Q000276:immunology; D015996:Survival Rate; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000473:pathology
chemical_list: D006684:HLA-DR Antigens; D018840:HSP70 Heat-Shock Proteins; D018841:HSP90 Heat-Shock Proteins; D018950:Lipopolysaccharide Receptors; C106644:SOCS3 protein, human; D000071223:Suppressor of Cytokine Signaling 3 Protein
keywords: HLA-DR; Heat shock proteins; Immunoparalysis; SIRS; SOCS; Sepsis