title: Reduced Responsiveness of Blood Leukocytes to Lipopolysaccharide Does not Predict Nosocomial Infections in Critically Ill Patients.
abstract: Critically ill patients show signs of immune suppression, which is considered to increase vulnerability to nosocomial infections. Whole-blood stimulation is frequently used to test the function of the innate immune system. We here assessed the association between whole-blood leukocyte responsiveness to lipopolysaccharide (LPS) and subsequent occurrence of nosocomial infections in critically ill patients admitted to the intensive care unit (ICU). All consecutive critically ill patients admitted to the ICU between April 2012 and June 2013 with two or more systemic inflammatory response syndrome criteria and an expected length of ICU stay of more than 24 h were enrolled. Age- and sex-matched healthy individuals were included as controls. Blood was drawn the first morning after ICU admission and stimulated ex vivo with 100 ng/mL ultrapure LPS for 3 h. Tumor necrosis factor-α, interleukin-1β (IL-1β), and IL-6 were measured in supernatants. Seventy-three critically ill patients were included, of whom 10 developed an ICU-acquired infection. Compared with healthy subjects, whole-blood leukocytes of patients were less responsive to ex vivo stimulation with LPS, as reflected by strongly reduced tumor necrosis factor-α, IL-1β, and IL-6 levels in culture supernatants. Results were not different between patients who did and those who did not develop an ICU-acquired infection. The extent of reduced LPS responsiveness of blood leukocytes in critically ill patients on the first day after ICU admission does not relate to the subsequent development of ICU-acquired infections. These results argue against the use of whole-blood stimulation as a functional test applied early after ICU admission to predict nosocomial infection.
authors.affiliation: *Center for Experimental and Molecular Medicine, †Department of Intensive Care, and ‡Division of Infectious Diseases, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: Lonneke A
authors.initials: LA
authors.lastname: van Vught
authors.forename: Maryse A
authors.initials: MA
authors.lastname: Wiewel
authors.forename: Arie J
authors.initials: AJ
authors.lastname: Hoogendijk
authors.forename: Brendon P
authors.initials: BP
authors.lastname: Scicluna
authors.forename: Hakima
authors.initials: H
authors.lastname: Belkasim-Bohoudi
authors.forename: Janneke
authors.initials: J
authors.lastname: Horn
authors.forename: Marcus J
authors.initials: MJ
authors.lastname: Schultz
authors.forename: Tom
authors.initials: T
authors.lastname: van der Poll
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D016638:Critical Illness; D003428:Cross Infection / Q000097:blood* / Q000175:diagnosis*; D005260:Female; D006801:Humans; D007107:Immune System; D007362:Intensive Care Units; D053583:Interleukin-1beta / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D007962:Leukocytes / Q000187:drug effects*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: C508585:IL1B protein, human; C508600:IL6 protein, human; D053583:Interleukin-1beta; D015850:Interleukin-6; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha