title: One week of multifactorial high-stress military ranger training affects Gram-negative signalling.
abstract: BACKGROUND
  Toll-like receptor 4 (TLR4), especially expressed on monocytes/macrophages, connects microbial and sterile innate immune activation. Lipopolysaccharide (LPS) from Gram-negative bacteria and several endogenous molecules, among others saturated fatty acids (SFAs), are able to induce signalling through this receptor. Downstream inflammatory cytokines orchestrate the immune response. Our aim was to investigate how long-lasting multifactorial stress affects Gram-negative signalling and search for possible correlations between cytokine production and TLR4 expression or SFA concentration.
  
  
  METHODS
  Eight healthy males were studied during a 7-day ranger-training course with semi-continuous physical strain, together with energy and sleep restrictions. Blood drawn on days 0, 3, 5 and 7 was incubated ex vivo for 6 h with or without LPS 10 ng/mL, whereupon surface expression of TLR4 on CD14⁺ monocytes and supernatant concentrations of inflammatory cytokines (TNF-α, IL-1β and IL-6) were measured. In addition, plasma free fatty acids were quantified.
  
  
  RESULTS
  Monocyte TLR4 expression was elevated throughout the course (p < 0.05 vs. baseline). Corresponding results were found for SFAs. The concentration of TNF-α increased significantly on day 3 and thereafter normalized, and a similar pattern was seen for IL-1β. No correlations were found between cytokine concentrations and monocyte TLR4 expression or plasma SFAs.
  
  
  CONCLUSIONS
  Multifactorial stress significantly affected ex vivo production of TNF-α and monocyte surface expression of TLR4. In addition, mobilization of fat resulted in increased plasma concentrations of SFAs. No associations between inflammatory cytokines and monocyte TLR4 expression or SFAs were found.
authors.affiliation: Institute of Clinical Medicine, University of Oslo, Oslo, Norway. bard.lundeland@medisin.uio.no
authors.forename: Bård
authors.initials: B
authors.lastname: Lundeland
authors.forename: Yngvar
authors.initials: Y
authors.lastname: Gundersen
authors.forename: Per-Kristian
authors.initials: PK
authors.lastname: Opstad
authors.forename: Ingjerd
authors.initials: I
authors.lastname: Thrane
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Richard W
authors.initials: RW
authors.lastname: Olaussen
authors.forename: Per
authors.initials: P
authors.lastname: Vaagenes
mesh_terms: D005230:Fatty Acids, Nonesterified / Q000097:blood; D005434:Flow Cytometry; D006090:Gram-Negative Bacteria / Q000378:metabolism*; D006801:Humans; D008297:Male; D008889:Military Personnel; D015398:Signal Transduction; D013312:Stress, Physiological
chemical_list: D005230:Fatty Acids, Nonesterified