title: Lipopolysaccharide and toll-like receptor 4 in dogs with congenital portosystemic shunts.
abstract: Surgical attenuation of a congenital portosystemic shunt (CPSS) results in increased portal vein perfusion, liver growth and clinical improvement. Portal lipopolysaccharide (LPS) is implicated in liver regeneration via toll-like receptor (TLR) 4 mediated cytokine activation. The aim of this study was to investigate factors associated with LPS in dogs with CPSS. Plasma LPS concentrations were measured in the peripheral and portal blood using a limulus amoebocyte lysate (LAL) assay. LPS concentration was significantly greater in the portal blood compared to peripheral blood in dogs with CPSS (P = 0.046) and control dogs (P = 0.002). LPS concentrations in the peripheral (P = 0.012) and portal (P = 0.005) blood of dogs with CPSS were significantly greater than those of control dogs. The relative mRNA expression of cytokines and TLRs was measured in liver biopsies from dogs with CPSS using quantitative PCR. TLR4 expression significantly increased following partial CPSS attenuation (P = 0.020). TLR4 expression was significantly greater in dogs that tolerated complete CPSS attenuation (P = 0.011) and those with good portal blood flow on pre-attenuation (P = 0.004) and post-attenuation (P = 0.015) portovenography. Serum interleukin (IL)-6 concentration was measured using a canine specific ELISA and significantly increased 24 h following CPSS attenuation (P < 0.001). Portal LPS was increased in dogs with CPSS, consistent with decreased hepatic clearance. TLR4 mRNA expression was significantly associated with portal blood flow and increased following surgery. These findings support the concept that portal LPS delivery is important in the hepatic response to surgical attenuation. Serum IL-6 significantly increased following surgery, consistent with LPS stimulation via TLR4, although this increase might be non-specific.
authors.affiliation: Department of Veterinary Clinical Sciences, Royal Veterinary College, Hawkshead Lane, North Mymms, Hatfield, Hertfordshire AL9 7TA, UK. Electronic address: mickey.tivers@bristol.ac.uk.
authors.forename: M S
authors.initials: MS
authors.lastname: Tivers
authors.affiliation: Department of Veterinary Clinical Sciences, Royal Veterinary College, Hawkshead Lane, North Mymms, Hatfield, Hertfordshire AL9 7TA, UK.
authors.forename: V J
authors.initials: VJ
authors.lastname: Lipscomb
authors.affiliation: Department of Pathology and Infectious Diseases, Royal Veterinary College, Hawkshead Lane, North Mymms, Hatfield, Hertfordshire AL9 7TA, UK.
authors.forename: K C
authors.initials: KC
authors.lastname: Smith
authors.affiliation: Department of Comparative Biomedical Sciences, Royal Veterinary College, Royal College Street, London NW1 0TU, UK.
authors.forename: C P D
authors.initials: CP
authors.lastname: Wheeler-Jones
authors.affiliation: Veterinary Referral Hospital, 18/151-159 Princess Hwy, Hallam, Victoria, Australia.
authors.forename: A K
authors.initials: AK
authors.lastname: House
mesh_terms: D000818:Animals; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004285:Dogs / Q000002:abnormalities* / Q000601:surgery; D015850:Interleukin-6 / Q000097:blood; D008070:Lipopolysaccharides / Q000097:blood*; D008099:Liver / Q000378:metabolism; D011169:Portal Vein / Q000002:abnormalities* / Q000601:surgery; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction / Q000662:veterinary; D051197:Toll-Like Receptor 4 / Q000378:metabolism*; D054079:Vascular Malformations / Q000378:metabolism / Q000601:surgery / Q000662:veterinary*
chemical_list: D016207:Cytokines; D015850:Interleukin-6; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D051197:Toll-Like Receptor 4
keywords: Congenital portosystemic shunts; Dog; IL-6; Lipopolysaccharide; Liver; Toll like receptor 4