title: Neonatal immune challenge exacerbates experimental colitis in adult rats: potential role for TNF-alpha.
abstract: Early life events and childhood infections have been associated with the development and onset of inflammatory bowel disease in adulthood. However, the consequences of neonatal infection in the development and severity of colitis are not established. We investigated the effects of a neonatal (postnatal day 14) or juvenile (postnatal day 28) immune challenge with LPS on 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced damage and weight loss, as well as on food intake and body temperature in adult rats. Neonatally (n)LPS-treated rats developed more severe colitis than control animals, reflected in a greater loss of weight and a significantly increased macroscopic tissue damage score. These findings were associated with a hypothermic response after TNBS treatment in nLPS rats, but not in neonatally saline-treated rats receiving TNBS. These differences were not seen after TNBS in rats that had received LPS on postnatal day 28. Plasma corticosterone was measured as an index of adult hypothalamic-pituitary-adrenal (HPA) axis activation as was TNF-alpha, a proinflammatory cytokine associated with inflammatory bowel disease. Four days after TNBS treatment, plasma corticosterone was unaltered in all groups; however, TNF-alpha was significantly increased in adult TNBS-treated rats that had LPS as neonates compared with all other groups. In conclusion, neonatal, but not later, exposure to LPS produces long-term exacerbations in the development of colitis in adults. This change is independent of HPA axis activation 4 days after TNBS treatment but is associated with increased circulating TNF-alpha, suggestive of an exaggerated immune response in adults exposed to neonatal infection.
authors.affiliation: Hotchkiss Brain Institute and Institute of Infection, Immunity, and Inflammation, Department of Physiology and Biophysics, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada. spences@ucalgary.ca
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Spencer
authors.forename: Niall P
authors.initials: NP
authors.lastname: Hyland
authors.forename: Keith A
authors.initials: KA
authors.lastname: Sharkey
authors.forename: Quentin J
authors.initials: QJ
authors.lastname: Pittman
mesh_terms: D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D001831:Body Temperature / Q000502:physiology; D002940:Circadian Rhythm / Q000502:physiology; D003092:Colitis / Q000139:chemically induced* / Q000276:immunology* / Q000473:pathology; D003345:Corticosterone / Q000097:blood; D005260:Female; D007109:Immunity / Q000187:drug effects*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D014302:Trinitrobenzenesulfonic Acid / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*; D015431:Weight Loss / Q000502:physiology
chemical_list: D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D014302:Trinitrobenzenesulfonic Acid; D003345:Corticosterone