Interleukin-12 induces mild experimental allergic encephalomyelitis following local central nervous system injury in the Lewis rat.
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.
Ahmed
Zubair
Z
Department of Neuroinflammation, Institute of Neurology, University College London, Queen Square, London, WC1N 3BG, UK. z.ahmed.l@bham.ac.uk
Baker
David
D
Cuzner
M Louise
ML
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
D011994:Recombinant Proteins; D018664:Interleukin-12; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C496318:Nos2 protein, rat