title: Hemoadsorption reprograms inflammation in experimental gram-negative septic peritonitis: insights from in vivo and in silico studies.
abstract: Improper compartmentalization of the inflammatory response leads to systemic inflammation in sepsis. Hemoadsorption (HA) is an emerging approach to modulate sepsis-induced inflammation. We sought to define the effects of HA on inflammatory compartmentalization in Escherichia coli-induced fibrin peritonitis in rats.
  
  
  OBJECTIVE
  HA both reprograms and recompartmentalizes inflammation in sepsis. Sprague Dawley male rats were subjected to E. coli peritonitis and, after 24 h, were randomized to HA or sham treatment (sepsis alone). Venous blood samples collected at 0, 1, 3 and 6 h (that is, 24-30 h of total experimental sepsis), and peritoneal samples collected at 0 and 6 h, were assayed for 14 cytokines along with NO(2)(-/)NO(3)(-). Bacterial counts were assessed in the peritoneal fluid at 0 and 6 h. Plasma tumor necrosis factor (TNF)-α, interleukin (IL)-6, CXCL-1, and CCL2 were significantly reduced in HA versus sham. Principal component analysis (PCA) suggested that inflammation in sham was driven by IL-6 and TNF-α, whereas HA-associated inflammation was driven primarily by TNF-α, CXCL-1, IL-10 and CCL2. Whereas -peritoneal bacterial counts, plasma aspartate transaminase levels and peritoneal IL-5, IL-6, IL-18, interferon (IFN)-γ and NO(2)(-)/NO(3)(-) were significantly lower, both CXCL-1 and CCL2 as well as the peritoneal-to-plasma ratios of TNF-α, CXCL-1 and CCL2 were significantly higher in HA versus sham, suggesting that HA-induced inflammatory recompartmentalization leads to the different inflammatory drivers discerned in part by PCA. In conclusion, this study demonstrates the utility of combined in vivo/in silico methods and suggests that HA exerts differential effects on mediator gradients between local and systemic compartments that ultimately benefit the host.
authors: Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, United States of America.
authors: Rami A
authors: RA
authors: Namas
authors: Rajaie
authors: R
authors: Namas
authors: Claudio
authors: C
authors: Lagoa
authors: Derek
authors: D
authors: Barclay
authors: Qi
authors: Q
authors: Mi
authors: Ruben
authors: R
authors: Zamora
authors: Zhiyong
authors: Z
authors: Peng
authors: Xiaoyan
authors: X
authors: Wen
authors: Morgan V
authors: MV
authors: Fedorchak
authors: Isabella E
authors: IE
authors: Valenti
authors: William J
authors: WJ
authors: Federspiel
authors: John A
authors: JA
authors: Kellum
authors: Yoram
authors: Y
authors: Vodovotz
mesh_terms: D000327:Adsorption; D000818:Animals; D015415:Biomarkers / Q000097:blood; D015169:Colony Count, Microbial; D019295:Computational Biology; D004926:Escherichia coli / Q000254:growth & development / Q000502:physiology*; D005337:Fibrin / Q000378:metabolism; D006440:Hemofiltration; D007249:Inflammation / Q000097:blood* / Q000150:complications / Q000382:microbiology; D018836:Inflammation Mediators / Q000097:blood; D008099:Liver / Q000473:pathology; D008297:Male; D010537:Peritoneum / Q000382:microbiology / Q000473:pathology; D010538:Peritonitis / Q000097:blood* / Q000150:complications / Q000382:microbiology*; D025341:Principal Component Analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D018805:Sepsis / Q000097:blood* / Q000150:complications / Q000382:microbiology*
chemical_list: D015415:Biomarkers; D018836:Inflammation Mediators; D005337:Fibrin