title: Acute colitis chronically alters immune infiltration mechanisms and sensory neuro-immune interactions.
abstract: OBJECTIVE
  Little is understood regarding how disease progression alters immune and sensory nerve function in colitis. We investigated how acute colitis chronically alters immune recruitment and the impact this has on re-activated colitis. To understand the impact of disease progress on sensory systems we investigated the mechanisms underlying altered colonic neuro-immune interactions after acute colitis.
  
  
  METHODS
  Inflammation was compared in mouse models of health, acute tri-nitrobenzene sulphonic acid (TNBS) colitis, Remission and Reactivated colitis. Cytokine concentrations were compared by ELISA in-situ and in explanted colon tissue. Colonic infiltration by CD11b/F4-80 macrophage, CD4 THELPER(TH) and CD8 TCYTOTOXIC(TC) and α4β7expression on mesenteric lymph node (MLN) THand TCwas determined by flow cytometry. Cytokine and effector receptor mRNA expression was determined on colo-rectal afferent neurons and the mechanisms underlying cytokinergic effects on high-threshold colo-rectal afferent function were investigated using electrophysiology.
  
  
  RESULTS
  Colonic damage, MPO activity, macrophage infiltration, IL-1β and IL-6 concentrations were lower in Reactivated compared to Acute colitis. THinfiltration and α4β7expression on THMLN was increased in Remission but not Acute colitis. IFN-γ concentrations, THinfiltration and α4β7expression on THand TCMLN increased in Reactivated compared to Acute colitis. Reactivated explants secreted more IL-1β and IL-6 than Acute explants. IL-6 and TNF-α inhibited colo-rectal afferent mechanosensitivity in Remission mice via a BKCadependent mechanism.
  
  
  CONCLUSIONS
  Acute colitis persistently alters immune responses and afferent nerve signalling pathways to successive episodes of colitis. These findings highlight the complexity of viscero-sensory neuro-immune interactions in painful remitting and relapsing diseases.
authors.affiliation: Centre for Nutrition and Gastrointestinal Diseases, University of Adelaide and South Australian Health and Medical Research Institute (SAHMRI), Adelaide, Australia.
authors.forename: Melissa A
authors.initials: MA
authors.lastname: Campaniello
authors.affiliation: Centre for Nutrition and Gastrointestinal Diseases, University of Adelaide and South Australian Health and Medical Research Institute (SAHMRI), Adelaide, Australia.
authors.forename: Chris
authors.initials: C
authors.lastname: Mavrangelos
authors.affiliation: Centre for Nutrition and Gastrointestinal Diseases, University of Adelaide and South Australian Health and Medical Research Institute (SAHMRI), Adelaide, Australia; Department of Pharmacology, University of Adelaide, Adelaide, Australia.
authors.forename: Samuel
authors.initials: S
authors.lastname: Eade
authors.affiliation: Centre for Nutrition and Gastrointestinal Diseases, University of Adelaide and South Australian Health and Medical Research Institute (SAHMRI), Adelaide, Australia.
authors.forename: Andrea M
authors.initials: AM
authors.lastname: Harrington
authors.affiliation: Centre for Neuroscience and Trauma, Blizard Institute, Barts and the London School of Medicine & Dentistry, Queen Mary University of London, UK.
authors.forename: L Ashley
authors.initials: LA
authors.lastname: Blackshaw
authors.affiliation: Centre for Nutrition and Gastrointestinal Diseases, University of Adelaide and South Australian Health and Medical Research Institute (SAHMRI), Adelaide, Australia.
authors.forename: Stuart M
authors.initials: SM
authors.lastname: Brierley
authors.affiliation: Department of Pharmacology, University of Adelaide, Adelaide, Australia.
authors.forename: Scott D
authors.initials: SD
authors.lastname: Smid
authors.affiliation: Centre for Nutrition and Gastrointestinal Diseases, University of Adelaide and South Australian Health and Medical Research Institute (SAHMRI), Adelaide, Australia. Electronic address: patrick.hughes@adelaide.edu.au.
authors.forename: Patrick A
authors.initials: PA
authors.lastname: Hughes
mesh_terms: D000208:Acute Disease; D000818:Animals; D003092:Colitis / Q000276:immunology*; D003106:Colon / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D007249:Inflammation / Q000276:immunology*; D008264:Macrophages / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D009475:Neurons, Afferent / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D016207:Cytokines; D014409:Tumor Necrosis Factor-alpha
keywords: Inflammatory Bowel Disease; Irritable Bowel Syndrome; Neural-immune interactions; TNBS-induced colitis; Visceral nociception