title: Hyperchloremic acidosis increases circulating inflammatory molecules in experimental sepsis.
abstract: BACKGROUND
  Hyperchloremic acidosis is common in the critically ill and is often iatrogenic. We have previously shown that hyperchloremic acidosis increases nuclear factor-kappaB DNA binding in lipopolysaccharide-stimulated RAW 264.7 cells. However, evidence that hyperchloremic acidosis leads to increased inflammation in vivo has been limited to nitric oxide.
  
  
  OBJECTIVE
  To determine if acidosis, induced by dilute hydrochloric acid (HCl) infusion, will increase circulating inflammatory mediator levels in an experimental model of severe sepsis in rats.
  
  
  METHODS
  Eighteen hours after inducing lethal sepsis by cecal ligation and puncture in 20 adult, male, Sprague-Dawley rats, we randomized animals into three groups. In groups 2 and 3, we began an IV infusion of 0.1 N HCl to reduce the standard base excess (SBE) by 5 to 10 mEq/L and 10 to 15 mEq/L, respectively. In group 1, we infused a similar volume of lactated Ringer solution. In all groups infusion continued 8 h or until the animal died.
  
  
  RESULTS
  We measured arterial blood gases, whole-blood lactate, and chloride, tumor necrosis factor (TNF), interleukin (IL)-6, and IL-10 levels at 0 h, 4 h, and 8 h. All measured cytokines increased over time. Compared to group 1, animals in groups 2 and 3 exhibited greater increase in all three cytokines, with the greatest increases seen with severe acidosis.
  
  
  CONCLUSIONS
  Moderate (SBE, - 5 to - 10) and severe (SBE, - 10 to - 15) acidosis, induced by HCl infusion, increases circulating levels of IL-6, IL-10, and TNF in normotensive septic rats.
authors.affiliation: University of Pittsburgh, School of Medicine, Department of Critical Care Medicine, 3550 Terrace St, Pittsburgh, PA 15261, USA. Kellumja@ccm.upmc.edu
authors.forename: John A
authors.initials: JA
authors.lastname: Kellum
authors.forename: Mingchen
authors.initials: M
authors.lastname: Song
authors.forename: Eyad
authors.initials: E
authors.lastname: Almasri
mesh_terms: D000136:Acid-Base Equilibrium / Q000187:drug effects / Q000276:immunology; D000138:Acidosis / Q000139:chemically induced / Q000276:immunology*; D000818:Animals; D001794:Blood Pressure; D002712:Chlorides / Q000097:blood*; D004797:Enzyme-Linked Immunosorbent Assay; D005440:Fluid Therapy; D006851:Hydrochloric Acid; D018836:Inflammation Mediators / Q000097:blood*; D016753:Interleukin-10 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012772:Shock, Septic / Q000139:chemically induced / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D002712:Chlorides; D018836:Inflammation Mediators; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D006851:Hydrochloric Acid