Cytokine‐induced enhancement of autoimmune inflammation in the brain and spinal cord: implications for multiple sclerosis

Neuropathology and Applied Neurobiology - Tập 30 Số 4 - Trang 374-384 - 2004
Dong Sun1,2, Tracey A. Newman3,2, V. Hugh Perry3, Roy O. Weller2
1Current address: Medical College of Virginia, Virginia Commonwealth University, Richmond, VA, USA.
2Pathology and Clinical Neurosciences (Neuropathology), and
3CNS Inflammation Group, University of Southampton, Southampton, UK

Tóm tắt

Multiple sclerosis and experimental autoimmune encephalomyelitis (EAE) are autoimmune inflammatory diseases in which cytokines are intimately involved. Here we test the hypothesis that injection of pro‐inflammatory cytokines, tumour necrosis factor‐α (TNFα) and interferon gamma (IFNγ) into the brain of animals in the prodromal phase of EAE significantly enhances inflammation in the central nervous system (CNS). We were particularly interested to learn whether a local increase in cytokines influenced the pathology locally, or more extensively, within the CNS. EAE was induced in female adult Lewis rats. Eight days post‐inoculation, TNFα or INFγ was injected into one cerebral hemisphere. Days 11 and 13 post‐inoculation (3 and 5 days after the injection of cytokine) inflammation was quantified by the number of perivascular cuffs and the degree of major histocompatibility complex (MHC) class II expression by microglia. Normal animals injected with cytokines, and EAE animals with saline injection served as controls. Results: microglial activation was increased three‐ to fourfold in the brain and eightfold in the spinal cord (P ≤ 0.05); lymphocyte invasion was increased sixfold in the brain and three‐ to fourfold in the spinal cord (P ≤ 0.01) following injections of TNFα or INFγ in EAE animals compared with controls. Significant axonal damage was observed in white matter associated with the perivascular cuffs. Conclusion: local changes in the release of pro‐inflammatory cytokines within the brain in EAE results in the widespread enhancement of autoimmune inflammation within the brain and cord, and exacerbation of clinical symptoms.

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Tài liệu tham khảo

10.1016/S0140-6736(02)08220-X

10.1093/brain/120.3.393

Prineas JW, 2002, Greenfields Neuropathology., 471

Vass K, 1990, Intrathecal application of interferon gamma. Progressive appearance of MHC antigens within the rat nervous system, Am J Pathol, 137, 789

10.1002/ana.410370710

10.1002/ana.410360716

10.1002/(SICI)1096-9896(199708)182:4<457::AID-PATH870>3.0.CO;2-Y

10.1111/j.1365-2990.1995.tb01050.x

10.1097/00019052-199906000-00008

10.1111/j.1750-3639.1992.tb00703.x

10.1046/j.1365-2990.1999.00165.x

10.1002/(SICI)1096-9896(199901)187:2<259::AID-PATH212>3.0.CO;2-H

10.1093/jnen/59.12.1031

10.1007/BF00281860

Feuerstein GZ, 1994, Cytokines, inflammation, and brain injury: role of tumor necrosis factor‐alpha, Cerebrovasc Brain Metab Rev, 6, 341

10.1016/0165-5728(92)90216-8

10.1016/S0301-0082(02)00010-2

10.4049/jimmunol.134.6.3785

10.1002/(SICI)1097-4547(19960501)44:3<223::AID-JNR3>3.0.CO;2-I

10.1016/S0065-2776(08)60428-9

Glabinski A, 1998, Tumor necrosis factor‐alpha induced pathology in the rat brain: characterization of stereotaxic injection model, Folia Neuropathol, 36, 52

10.1016/0092-8674(94)90337-9

10.1093/brain/120.3.435

10.1016/0165-5728(91)90121-M

10.1016/S0140-6736(85)92801-6

10.1002/jemt.1070320402

10.1007/BF00294613

Molleston MC, 1993, Novel major histocompatibility complex expression by microglia and site‐specific experimental allergic encephalomyelitis lesions in the rat central nervous system after optic nerve transection, Adv Neurol, 59, 337

10.1097/00005072-199903000-00004

10.1016/S0306-4522(00)00403-6

10.1002/eji.1830260735

10.4049/jimmunol.164.9.4481

10.1006/mcne.1998.0725

10.1002/(SICI)1521-4141(199903)29:03<774::AID-IMMU774>3.0.CO;2-T

10.1084/jem.186.9.1585

Rothwell NJ, 1993, Involvement of interleukin‐1 and lipocortin‐1 in ischaemic brain damage, Cerebrovasc Brain Metab Rev, 5, 178

Blatteis CM, 2000, The afferent signalling of fever, J Physiol, 526, 470

10.1111/j.1749-6632.2002.tb04198.x

10.1016/S0165-5728(03)00134-6

10.1016/S1010-7940(01)00841-7

10.1093/brain/awf098

10.1136/bmj.327.7416.646

10.1007/BF00194101

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Neuropathology and Applied Neurobiology

Tập 30 Số 4

374-384

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