title: Primed monocytes: putative culprits of chronic low-grade inflammation and impaired innate immune responses in patients on hemodialysis.
abstract: BACKGROUND
  End-stage renal disease patients are known to be in a state of chronic low-grade inflammation and to have high infection-related morbidity and mortality. However, the precise mechanisms are not understood. The purpose of this study was to determine the mechanisms underlying chronic low-grade inflammation and defects in innate immune responses in hemodialysis (HD) patients.
  
  
  METHODS
  In 33 HD patients, we measured the basal status of toll-like receptor 4 (TLR4) positivity in the CD14-positive monocyte population in the peripheral blood (not strong, i.e., CD14(low)), with plasma levels of tumor necrosis factor (TNF)-α and interleukin (IL)-1β, IL-6, IL-8, IL-10, and IL-12p70 compared with 22 healthy controls. After stimulation by lipopolysaccharide (LPS), the plasma cytokine response was also compared.
  
  
  RESULTS
  In the basal state, the percentage of peripheral blood TLR4(+)CD14(low) monocytes and plasma cytokines were significantly higher in HD patients (p < 0.05), suggesting that preactivated primed monocytes might be responsible for the chronic inflammatory state in HD patients. However, upon LPS challenge, the fold increase in plasma cytokine response was significantly reduced in HD patients (p < 0.05) compared with controls. More importantly, the fold increase of these cytokines showed a positive correlation with plasma albumin (p < 0.05) and a negative correlation with C-reactive protein (CRP) (p < 0.05), suggesting the presence of a possible link between chronic low-grade inflammation and suboptimal innate immune response.
  
  
  CONCLUSIONS
  Chronic low-grade inflammation due to preactivated peripheral blood CD14(+) leukocyte subset might be a mechanism for impaired innate immune responses, thus resulting in the high rates of infection-related morbidity and mortality observed in HD patients.
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Korea University Anam Hospital, Korea University College of Medicine, Seoul, Korea.
authors.forename: Hye Won
authors.initials: HW
authors.lastname: Kim
authors.forename: Young Seok
authors.initials: YS
authors.lastname: Woo
authors.forename: Ha Na
authors.initials: HN
authors.lastname: Yang
authors.forename: Hye Min
authors.initials: HM
authors.lastname: Choi
authors.forename: Sang Kyung
authors.initials: SK
authors.lastname: Jo
authors.forename: Won Yong
authors.initials: WY
authors.lastname: Cho
authors.forename: Hyoung-Kyu
authors.initials: HK
authors.lastname: Kim
mesh_terms: D002097:C-Reactive Protein / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D006801:Humans; D007113:Immunity, Innate; D007249:Inflammation / Q000276:immunology*; D007676:Kidney Failure, Chronic / Q000276:immunology; D018950:Lipopolysaccharide Receptors / Q000097:blood; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology*; D006435:Renal Dialysis / Q000009:adverse effects*; D012709:Serum Albumin; D051197:Toll-Like Receptor 4
chemical_list: D016207:Cytokines; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D012709:Serum Albumin; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D002097:C-Reactive Protein