Basic Medical Sciences and Clinics (3) (Alzhe2 ,,, MHC, , AD PD T CD 4. Th (T0) T0

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1 200 Basic Medical Sciences and Clinics (3) : (2002) ,, 3 (, ) : (Alzheimer s disease, AD) (Parkinson s disease, PD),, : ; ; ; :R :A (Alzhe2 imer s disease, AD) ( Parkinson s disease, PD),,AD PD 1,,, [1 ],,,,,,, [2 ],,, T CD 4 + Th (T0) T0, : Th1 Th2 [3 ] Th1,,,, Th2 2 (TGF2 ) 24 ( IL24) 210 ( IL2 10), B, Th1,, [4 ] ( 1) Th1 Th2 : (MHC),, MHC, [5 ] 2, AD PD [6 ] : : ( G ) 3

2 (3) Basic Medical Sciences and Clinics 201,, mrna, 1 Fig 1 The activation of immune system and the effects of cytokines on neuron and glial cell [7 ], [8 ], 211,, [13 ],, HIV AD,,,,,,, [14 ], 212 [9 ], ; :,,, ;,,, [15 ],,,, CR 3 MHC, [10 ], [11 ] 1 2d [12 ]

3 202 Basic Medical Sciences and Clinics (3), 2 ( TNF2 ) 21 ( IL21) 2 ( IFN2 ) TNF2 17KD, AD TNF2 AD : MHC, MHC ( senile plaques, SP) T (neurofibrillary tangles, NFT) SP,TNF2, ; TNF2 NO, Tau (colony stimulat2, ing factors,csf) [16 ] CSF AD AD,,, :AD A,, TNF2 A,, TNF2 Ca 2 +, [17 ] IL21 17KD, IL21 IL21,,,, MHC, T0, T0 26 % : IL21 B, PD IL21 A, ;, IL21, Tc,Tc, [20 ] AD, ; A A,,IL21 T,, IL21 : [21 ], ; A, A (nitric oxide, NO) ; Ca 2 + [18 ] A, IFN2,, 14 25kD AD,,A IFN2, MHC ; inos (inducible ni2 AD A tric oxide synthase, inos), NO, IFN2, MHC, AD : A T, IFN2 A, IFN2, AD [19 ] 3 311

4 (3) Basic Medical Sciences and Clinics 203 A, A, A,, A, A,,, : IgG, [22 ] :A, A A ; A, A,,A A ; A A, Fc, A [23,24 ],AD,, NF2 B,, [25 ] 312 PD,, Lewy DA DA,,, PD [26 ] PD Nagatsu PD PD, :PD ; ;PD,,,,,PD, 20, 95 %, 80 %, 5 %,,PD,,, : ; ; DA [27 ] 4, NO,, NF2 B, ; TNF2 IL21, IL26 camp,, NF2 B [28 ] TNF2,

5 204 Basic Medical Sciences and Clinics (3), camp [29 ] (naloxone),, (LPS) TNF2 NO, LPS, [30 ] NF2 B, NF2 B I B,, I B, NF2 B, I B,, NF2 B [31 ], A AD,, : [1 ] Miller DW. Immunobiology of the blood2brain barrier [ J ]. J Neurovirol, 1999, 5 : [2 ] Lawrence DA, Kim D. CentralΠperipheral nervous system and immune responses[j ]. Toxicology, 2000,142 : [3 ] Romagnani S. T2cell subsets (Th1 versus Th2) [J ]. Ann Al2 lergy Asthma Immunol, 2000, 85 : [ 4 ] Romagnani Sestet. Th1ΠTh2 cells [ J ]. Inflamm Bowel Dis, 1999, 5 : [5 ] Streit WJ, Walter SA, Pennell NA. Reactive microgliosis[j ]. Prog Neurobiol, 1999, 57 : [6 ] Martino G, Furlan R, Brambilla E, et al. Cytokines and im2 munity in multiple sclerosis : the dual signal hypothesis[j ]. J Neuroimmunol, 2000,109 :3-9. [ 7 ] Pocock JM, Liddle AC. Microglial signalling cascades in neuro2 degenerative disease [J ]. Prog Brain Res, 2001, 132 : [ 8 ] Brod SA. Unregulated inflammation shortens human functional longevity[j ]. Inflamm Res, 2000, 49 : [ 9 ] Banati RB, Gehrmann J, Schubert P, et al. Cytotoxicity of mi2 croglia[j ]. Glia, 1993, 7 : [10 ] Gehrmann J, Schoen SW, Kreutzberg GW. Lesion of the rat entorhinal cortex leads to a rapid microglial reaction in the dentate gyrus. A light and electron microscopical study [J ]. Acta Neuropathol (Berl), 1991, 82 : [11 ] Chung IY, Benveniste EN. Tumor necrosis factor2alpha pro2 duction by astrocytes. Induction by lipopolysaccharide, IFN2 gamma, and IL21 beta [J ]. J Immunol, 1990, 144 : [12 ] Streit WJ, Semple2Rowland SL, Hurley SD, et al. Cytokine mrna profiles in contused spinal cord and axotomized facial nucleus suggest a beneficial role for inflammation and gliosis [J ]. Exp Neurol, 1998, 152 : [13 ] Fagan AM, Gage FH. Cholinergic sprouting in the hippocam2 pus : a proposed role for IL21 [J ]. Exp Neurol, 1990, 110 : [ 14 ] Benveniste EN. Cytokines : influence on glial cell gene expres2 sion and function[j ]. Chem Immunol, 1997, 69 : [15 ] Paludan SR. Synergistic action of pro2inflammatory agents : cellular and molecular aspects[j ]. J Leukoc Biol, 2000, 67 : [16 ] Benveniste EN, Kwon J, Chung WJ, et al. Differential modu2 lation of astrocyte cytokine gene expression by TGF2beta[J ]. J Immunol, 1994,153 : [17 ] Tweardy DJ, Glazer EW, Mott PL, et al. Modulation by tu2 mor necrosis factor2alpha of human astroglial cell production of granulocyte2macrophage colony2stimulating factor ( GM2CSF) and granulocyte colony2stimulating factor ( G2CSF) [ J ]. J Neuroimmunol, 1991, 32 : [18 ] Logan A. CNS growth factors[j ]. Br J Hosp Med, 1990, 43 : [19 ] Eneroth A, Andersson T, Olsson T, et al. Interferon2gamma2 like immunoreactivity in sensory neurons may influence the replication of Sendai and mumps viruses[j ]. J Neurosci Res, 1992, 31 :

6 (3) Basic Medical Sciences and Clinics 205 [20 ] Hock CH, Heese K, Olivieri G, et al. Alterations in neuro2 trophins and neurotrophin receptors in Alzheimer s disease [J ]. J Neural Transm Suppl, 2000, 59 : [21 ] Weller RO, Massey A, Kuo YM, et al. Cerebral amyloid an2 giopathy: accumulation of A beta in interstitial fluid drainage pathways in Alzheimer s disease [J ]. Ann N Y Acad Sci, 2000, 903 : [22 ] Schenk D, Barbour R, Dunn W, et al. Immunization with amyloid2beta attenuates Alzheimer2disease2like pathology in the PDAPP mouse[j ]. Nature, 1999,400 : [23 ] Barinaga M. An immunization against Alzheimer s? [J ]. Sci2 ence, 1999,285 :175, 177. [24 ] St George2Hyslop PH, Westaway DA. Alzheimer s disease. Antibody clears senile plaques[j ]. Nature, 1999, 400 : [25 ] Duff K. Curing amyloidosis : will it work in humans? [J ]. Trends Neurosci, 1999, 22 : [26 ] Bas J, Calopa M, Mestre M, et al. Lymphocyte populations in Parkinson s disease and in rat models of parkinsonism[j ]. J Neuroimmunol, 2001, 113 : [ 27 ] Benveniste EN. Inflammatory cytokines within the central ner2 vous system : sources, function, and mechanism of action[j ]. Am J Physio, 1992, 263 :1-16. [28 ] Fiebch BL, Hofer TJ, Lieb K, et al. The non2steroidal anti2 inflammatory drug tepoxalin inhibits interleukin26 and alpha12 anti2chymotrypsin synthesis in astrocytes by preventing degra2 dation of I B2alpha[J ]. Neuropharmacology, 1999, 38 : [29 ] Kim WK, Kan Y, Ganea D, et al. Vasoactive Intestinal Pep2 tide and Pituitary Adenylyl ccyclase2activating Polypeptide In2 hibit Tumor Necrosis Factor2 Production in Injured Spinal Cord and in Activated Microglia via a camp2dependent Path2 way[j ]. J Neurosci, 2000,20 : [ 30 ] Liu B, Jiang JW, Wilson BC, et al. Systemic infusion of nal2 oxone reduces degeneration of rat substantia nigral dopaminer2 gic neurons induced by intranigral injection of lipopolysac2 charide[j ]. J Pharmacol Exp Ther, 2000, 295 : [31 ] Epinat JC and Gilmore TD. Diverse agents act at multiple lev2 els to inhibit the RelΠNF2 B signal transduction pathway[j ]. Oncogene,1999,18 : Abnormal immune response and degenerative diseases of central nervous system ZHOU Hui2fang, XUE Bin, WANG Xiao2min (Neuroscience Research Institute, Peking University, Beijing , China) Abstract : Immune responses may play an active role in the pathogenesis of central nervous system ( CNS) degenerative diseases such as Alzheimer s disease (AD) and Parkinson s disease ( PD). Activated microglia can secrete neurotoxic factors, such as active oxygen intermediates, nitric oxide and proinflammatoy cytokines. The uncontrolled production of proinflammatory cytokines may cause the damage. AD and PD are the common age2related neurodegenerative diseases. Immune response may be involved in the neurodegeneration in AD or PD. The deleterious effects of microglial activation probably represent a common event associated with neurodegeration. It highlighted potential targets for therapeutic leads, such as inhibition of cytokine production, cytokines binding to their receptors, and cytokines intracellular signaling path2 ways. Key words : neurodegenerative disease ; immune responses ; neurotoxic factors

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