title: Cardiac arrest patients have an impaired immune response, which is not influenced by induced hypothermia.
abstract: BACKGROUND
  Induced hypothermia is increasingly applied as a therapeutic intervention in ICUs. One of the underlying mechanisms of the beneficial effects of hypothermia is proposed to be reduction of the inflammatory response. However, a fear of reducing the inflammatory response is an increased infection risk. Therefore, we studied the effect of induced hypothermia on immune response after cardiac arrest.
  
  
  METHODS
  A prospective observational cohort study in a mixed surgical-medical ICU. Patients admitted at the ICU after surviving cardiac arrest were included and during 24 hours body temperature was strictly regulated at 33°C or 36°C. Blood was drawn at three time points: after reaching target temperature, at the end of the target temperature protocol and after rewarming to 37°C. Plasma cytokine levels and response of blood leucocytes to stimulation with toll-like receptor (TLR) ligands lipopolysaccharide (LPS) from Gram-negative bacteria and lipoteicoic acid (LTA) from Gram-positive bacteria were measured. Also, monocyte HLA-DR expression was determined.
  
  
  RESULTS
  In total, 20 patients were enrolled in the study. Compared to healthy controls, cardiac arrest patients kept at 36°C (n = 9) had increased plasma cytokines levels, which was not apparent in patients kept at 33°C (n = 11). Immune response to TLR ligands in patients after cardiac arrest was generally reduced and associated with lower HLA-DR expression. Patients kept at 33°C had preserved ability of immune cells to respond to LPS and LTA compared to patients kept at 36°C. These differences disappeared over time. HLA-DR expression did not differ between 33°C and 36°C.
  
  
  CONCLUSIONS
  Patients after cardiac arrest have a modest systemic inflammatory response compared to healthy controls, associated with lower HLA-DR expression and attenuated immune response to Gram-negative and Gram-positive antigens, the latter indicative of an impaired immune response to bacteria. Patients with a body temperature of 33°C did not differ from patients with a body temperature of 36°C, suggesting induced hypothermia does not affect immune response in patients with cardiac arrest.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT01020916, registered 25 November 2009.
authors: Charlotte J
authors: CJ
authors: Beurskens
authors: Janneke
authors: J
authors: Horn
authors: Anita M Tuip
authors: AM
authors: de Boer
authors: Marcus J
authors: MJ
authors: Schultz
authors: Ester Mm
authors: EM
authors: van Leeuwen
authors: Margreeth B
authors: MB
authors: Vroom
authors: Nicole P
authors: NP
authors: Juffermans
mesh_terms: D000704:Analysis of Variance; D001831:Body Temperature / Q000276:immunology; D016207:Cytokines / Q000097:blood / Q000276:immunology; D005260:Female; D015600:Glasgow Coma Scale; D006323:Heart Arrest / Q000276:immunology* / Q000628:therapy; D006801:Humans; D007036:Hypothermia, Induced / Q000009:adverse effects / Q000379:methods*; D007249:Inflammation / Q000276:immunology*; D007362:Intensive Care Units; D007962:Leukocytes / Q000276:immunology; D008070:Lipopolysaccharides / Q000097:blood / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009426:Netherlands; D011446:Prospective Studies; D051193:Toll-Like Receptors / Q000097:blood / Q000276:immunology
chemical_list: D016207:Cytokines; D008070:Lipopolysaccharides; D051193:Toll-Like Receptors