Interleukin-12 induces mild experimental allergic encephalomyelitis following local central nervous system injury in the Lewis rat

• Published in: Journal of neuroimmunology 2003-07, Vol.140 (1), p.109-117
• Main Authors: Ahmed, Zubair, Baker, David, Cuzner, M.Louise
• Format: Article
• Language: English
• Subjects: Animals; Brain Injuries - immunology; Brain Injuries - metabolism; Brain Injuries - pathology; CD4-Positive T-Lymphocytes - chemistry; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - pathology; Central nervous system; Craniotomy; Encephalomyelitis, Autoimmune, Experimental - immunology; Encephalomyelitis, Autoimmune, Experimental - metabolism; Encephalomyelitis, Autoimmune, Experimental - pathology; Enzyme Activation - immunology; Experimental allergic encephalomyelitis; Female; Inflammation; Injections, Intraperitoneal; Interleukin-12; Interleukin-12 - administration & dosage; Macrophages - chemistry; Macrophages - immunology; Macrophages - pathology; Mice; Microglia - chemistry; Microglia - immunology; Microglia - pathology; Nitric Oxide Synthase - metabolism; Nitric Oxide Synthase Type II; Rats; Rats, Inbred Lew; Recombinant Proteins - administration & dosage; Severity of Illness Index; Somatosensory Cortex - chemistry; Somatosensory Cortex - immunology; Somatosensory Cortex - pathology; Spinal Cord - chemistry; Spinal Cord - immunology; Spinal Cord - pathology; T cells
• ISSN: 0165-5728; 1872-8421
• DOI: 10.1016/S0165-5728(03)00180-2

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.