title: Interleukin-12 induces mild experimental allergic encephalomyelitis following local central nervous system injury in the Lewis rat.
abstract: The major pathological feature in the central nervous system (CNS) following traumatic brain injury is activation of microglia both around and distant from the injury site. Intraperitoneal administration of interleukin-12 (IL-12) after brain injury resulted in a 7% weight loss, clinical signs of mild EAE and significant myelin basic protein (MBP)-specific splenic cell proliferation. The extent of pathology, in terms of the number of inflammatory perivascular cuffs and activation of microglia was greatest if IL-12 was administered immediately compared to a week following brain injury, whether at one or two sites. Specifically immunostaining for MHC class II and iNOS on macrophages and microglia, ICAM-1 on endothelial cells and macrophages was observed around the site of injury. A degree of myelin processing was apparent from immunostaining of MBP in inflammatory cells distant from the lesion. Inflammatory cuffs comprising macrophages, activated microglia, CD4(+) T cells and iNOS(+) cells were also detected distant to the injury site in the medulla and spinal cord of animals treated with IL-12. These results suggest that immune-mediated events in which IL-12 production is stimulated as for example viral infection, superimposed on a brain injury, could provide a trigger for a MS-like pathology.
authors.affiliation: Department of Neuroinflammation, Institute of Neurology, University College London, Queen Square, London, WC1N 3BG, UK. z.ahmed.l@bham.ac.uk
authors.forename: Zubair
authors.initials: Z
authors.lastname: Ahmed
authors.forename: David
authors.initials: D
authors.lastname: Baker
authors.forename: M Louise
authors.initials: ML
authors.lastname: Cuzner
mesh_terms: D000818:Animals; D001930:Brain Injuries / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D015496:CD4-Positive T-Lymphocytes / Q000737:chemistry / Q000276:immunology / Q000473:pathology; D003399:Craniotomy; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D004789:Enzyme Activation / Q000276:immunology; D005260:Female; D007274:Injections, Intraperitoneal; D018664:Interleukin-12 / Q000008:administration & dosage*; D008264:Macrophages / Q000737:chemistry / Q000276:immunology / Q000473:pathology; D051379:Mice; D017628:Microglia / Q000737:chemistry / Q000276:immunology / Q000473:pathology; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D051381:Rats; D011917:Rats, Inbred Lew; D011994:Recombinant Proteins / Q000008:administration & dosage; D012720:Severity of Illness Index; D013003:Somatosensory Cortex / Q000737:chemistry / Q000276:immunology / Q000473:pathology; D013116:Spinal Cord / Q000737:chemistry / Q000276:immunology / Q000473:pathology
chemical_list: D011994:Recombinant Proteins; D018664:Interleukin-12; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C496318:Nos2 protein, rat