title: Immunohistochemical expression of proinflammatory cytokines IL-1β, IL-6, TNF-α and involvement of COX-2, quantitatively confirmed by Western blot analysis, in Wernicke's encephalopathy.
abstract: Selective cerebral vulnerability is a major consequence of Wernicke's encephalopathy (WE), in which focal areas of the brain exhibit symmetrical profound neuronal loss and accompanying gliosis, occurring most frequently in diencephalic regions such as the thalamus and the mammillary bodies. Many processes have been proposed to explain the selective cerebral vulnerability and the focal neuronal cell death in Wernicke's encephalopathy. There are several mechanisms which are common to the pathophysiology of encephalopathies caused by thiamine deficiency (TD). Recently, emphasis is being placed on deficit in mitochondrial oxidative metabolism, oxidative/nitrosative stress, and the release of proinflammatory cytokines such as IL-1β, IL-6, and tumor necrosis factor-α (TNF-α). Cyclooxygenase-2 (COX-2) plays major roles in regulating brain damage and inflammation. Here we present two fatal cases of non-alcohol associated WE. The immunohistochemical study revealed increased proinflammatory cytokine immunoreactivity in the neurons of the mammillary bodies and medial thalamus, and in the periaqueductal regions, compared with basal constitutive levels of expression in the frontal cortex. Positive (WE cases) and negative (immediate trauma deaths) case-controls were used to confirm the results. TD induced IL-1β proteins weakly, while moderate increase was observed for TNF-α and IL-6. Immunofluorescence analysis by confocal microscopy confirmed the staining results for immunoreactivity in WE brains. Further, the induction of proinflammatory cytokine protein expression levels was quantified by Western blot analysis.
authors.affiliation: Department of Forensic Pathology, University of Foggia, Ospedale Colonnello D'Avanzo, Italy.
authors.forename: Margherita
authors.initials: M
authors.lastname: Neri
authors.forename: Santina
authors.initials: S
authors.lastname: Cantatore
authors.forename: Cristoforo
authors.initials: C
authors.lastname: Pomara
authors.forename: Irene
authors.initials: I
authors.lastname: Riezzo
authors.forename: Stefania
authors.initials: S
authors.lastname: Bello
authors.forename: Emanuela
authors.initials: E
authors.lastname: Turillazzi
authors.forename: Vittorio
authors.initials: V
authors.lastname: Fineschi
mesh_terms: D000328:Adult; D015153:Blotting, Western; D051546:Cyclooxygenase 2 / Q000032:analysis / Q000096:biosynthesis*; D013505:Digestive System Surgical Procedures / Q000009:adverse effects; D017809:Fatal Outcome; D005455:Fluorescent Antibody Technique; D006801:Humans; D007150:Immunohistochemistry; D053583:Interleukin-1beta / Q000032:analysis / Q000096:biosynthesis*; D015850:Interleukin-6 / Q000032:analysis / Q000096:biosynthesis*; D008297:Male; D018613:Microscopy, Confocal; D008875:Middle Aged; D010289:Parenteral Nutrition, Total / Q000009:adverse effects; D011183:Postoperative Complications / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000096:biosynthesis*; D014899:Wernicke Encephalopathy / Q000473:pathology* / Q000503:physiopathology*
chemical_list: D053583:Interleukin-1beta; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D051546:Cyclooxygenase 2