Abstract
Neuroimmune pharmacology is a newly emerging field that intersects with neuroscience, immunology, and pharmacology and that is seeking avenues for translational research and better understanding of disease mechanisms. It focuses on the immunity of the central nervous system (CNS) which is greatly influenced by endogenous effectors, such as cytokines and neurotransmitters, and by exogenous substances, including therapeutic compounds, infectious pathogens, and drugs of abuse. In this article, we attempt to raise awareness of the pivotal discovery of how those mediators affect the immunity of the CNS in both physiological conditions and processes of certain mental illnesses, including psychiatric disorders, neurodegenerative diseases, and cerebral dysfunctions due to drugs of abuse. The abnormality in cytokine networks, neurotransmitter homeostasis, and other immune responses may be involved in the neuropathology associated with those mental illnesses, and the therapeutic effects of the potential treatments can be attributed, at least partially, to their immunomodulatory activities. However, the resulting inflammatory cytokines from certain treatments frequently cause psychiatric complications. In addition, the poor neuropathological outcomes frequently found among drug abusers with HIV-1 infection appear to be related to the neurotoxic and immunomodulatory effects of the drugs used. Importantly, glial cells, especially microglia and astrocytes, are key players in the immunomodulatory activities in the CNS, and the functioning CNS is largely dependent upon the reciprocal interactions between neurons and glial cells. Therefore, glia–neuron interactions have become a critical issue for further understanding the disease mechanism. From this review, readers will gain insights into the new field of neuroimmune pharmacology, with a focus on the impacts of CNS immunity on the mental illnesses.
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Aarum J, Sandberg K, Haeberlein SL, Persson MA (2003) Migration and differentiation of neural precursor cells can be directed by microglia. Proc Natl Acad Sci USA 100:15983–15988
Abbas AK, Murphy KM, Sher A (1996) Functional diversity of helper T lymphocytes. Nature 383:787–793
Akhondzadeh S, Tabatabaee M, Amini H, Ahmadi Abhari SA, Abbasi SH, Behnam B (2007) Celecoxib as adjunctive therapy in schizophrenia: a double-blind, randomized and placebo-controlled trial. Schizophr Res 90:179–185
Akhondzadeh S, Jafari S, Raisi F, Nasehi AA, Ghoreishi A, Salehi B, Mohebbi-Rasa S, Raznahan M, Kamalipour A (2009) Clinical trial of adjunctive celecoxib treatment in patients with major depression: a double blind and placebo controlled trial. Depress Anxiety 26:607–611
Akiyama K (1999) Serum levels of soluble IL-2 receptor alpha, IL-6 and IL-1 receptor antagonist in schizophrenia before and during neuroleptic administration. Schizophr Res 37:97–106
Aksenov MY, Aksenova MV, Nath A, Ray PD, Mactutus CF, Booze RM (2006) Cocaine-mediated enhancement of Tat toxicity in rat hippocampal cell cultures: the role of oxidative stress and D1 dopamine receptor. Neurotoxicology 27:217–228
Anthony IC, Bell JE (2008) The neuropathology of HIV/AIDS. Int Rev Psychiatry 20:15–24
Antinori A, Arendt G, Becker JT, Brew BJ, Byrd DA, Cherner M, Clifford DB, Cinque P, Epstein LG, Goodkin K, Gisslen M, Grant I, Heaton RK, Joseph J, Marder K, Marra CM, McArthur JC, Nunn M, Price RW, Pulliam L, Robertson KR, Sacktor N, Valcour V, Wojna VE (2007) Updated research nosology for HIV-associated neurocognitive disorders. Neurology 69:1789–1799
Aune TM, McGrath KM, Sarr T, Bombara MP, Kelley KA (1993) Expression of 5HT1a receptors on activated human T cells. Regulation of cyclic AMP levels and T cell proliferation by 5-hydroxytryptamine. J Immunol 151:1175–1183
Bassil N, Grossberg GT (2009) Novel regimens and delivery systems in the pharmacological treatment of Alzheimer’s disease. CNS Drugs 23:293–307
Ben Achour S, Pascual O (2010) Glia: the many ways to modulate synaptic plasticity. Neurochem Int (in press)
Benbernou N, Esnault S, Shin HC, Fekkar H, Guenounou M (1997) Differential regulation of IFN-gamma, IL-10 and inducible nitric oxide synthase in human T cells by cyclic AMP-dependent signal transduction pathway. Immunology 91:361–368
Berger JR, Avison M (2004) The blood brain barrier in HIV infection. Front Biosci 9:2680–2685
Berry CC, de la Fuente JM, Mullin M, Chu SW, Curtis AS (2007) Nuclear localization of HIV-1 tat functionalized gold nanoparticles. IEEE Trans Nanobioscience 6:262–269
Bilbo SD, Schwarz JM (2009) Early-life programming of later-life brain and behavior: a critical role for the immune system. Front Behav Neurosci 3:1–14
Block ML, Zecca L, Hong JS (2007) Microglia-mediated neurotoxicity: uncovering the molecular mechanisms. Nat Rev Neurosci 8:57–69
Bonfoco E, Krainc D, Ankarcrona M, Nicotera P, Lipton SA (1995) Apoptosis and necrosis: two distinct events induced, respectively, by mild and intense insults with N-methyl-d-aspartate or nitric oxide/superoxide in cortical cell cultures. Proc Natl Acad Sci USA 92:7162–7166
Cabral GA (2006) Drugs of abuse, immune modulation, and AIDS. J Neuroimmune Pharmacol 1:280–295
Cabral GA, Staab A (2005) Effects on the immune system. Handb Exp Pharmacol 168:385–423
Calabrese JR, Skwerer RG, Barna B, Gulledge AD, Valenzuela R, Butkus A, Subichin S, Krupp NE (1986) Depression, immunocompetence, and prostaglandins of the E series. Psychiatry Res 17:41–47
Capuron L, Ravaud A, Dantzer R (2001a) Timing and specificity of the cognitive changes induced by interleukin-2 and interferon-alpha treatments in cancer patients. Psychosom Med 63:376–386
Capuron L, Ravaud A, Gualde N, Bosmans E, Dantzer R, Maes M, Neveu PJ (2001b) Association between immune activation and early depressive symptoms in cancer patients treated with interleukin-2-based therapy. Psychoneuroendocrinology 26:797–808
Casassus P, Caillat-Vigneron N, Martin A, Simon J, Gallais V, Beaudry P, Eclache V, Laroche L, Lortholary P, Raphael M, Guillevin L, Lortholary O (2002) Treatment of adult systemic mastocytosis with interferon-alpha: results of a multicentre phase II trial on 20 patients. Br J Haematol 119:1090–1097
Cazzullo CL, Sacchetti E, Galluzzo A, Panariello A, Adorni A, Pegoraro M, Bosis S, Colombo F, Trabattoni D, Zagliani A, Clerici M (2002) Cytokine profiles in schizophrenic patients treated with risperidone: a 3-month follow-up study. Prog Neuropsychopharmacol Biol Psychiatry 26:33–39
Chana G, Everall IP, Crews L, Langford D, Adame A, Grant I, Cherner M, Lazzaretto D, Heaton R, Ellis R, Masliah E (2006) Cognitive deficits and degeneration of interneurons in HIV+ methamphetamine users. Neurology 67:1486–1489
Collantes-Estevez E, Fernandez-Perez C (2003) Improved control of osteoarthritis pain and self-reported health status in non-responders to celecoxib switched to rofecoxib: results of PAVIA, an open-label post-marketing survey in Spain. Curr Med Res Opin 19:402–410
Cosenza MA, Zhao ML, Si Q, Lee SC (2002) Human brain parenchymal microglia express CD14 and CD45 and are productively infected by HIV-1 in HIV-1 encephalitis. Brain Pathol 12:442–455
Cysique LA, Brew BJ (2009) Neuropsychological functioning and antiretroviral treatment in HIV/AIDS: a review. Neuropsychol Rev 19:169–185
Dhillon NK, Williams R, Callen S, Zien C, Narayan O, Buch S (2008) Roles of MCP-1 in development of HIV-dementia. Front Biosci 13:3913–3918
Donahoe RM, O’Neil SP, Marsteller FA, Novembre FJ, Anderson DC, Lankford-Turner P, McClure HH (2009) Probable deceleration of progression of Simian AIDS affected by opiate dependency: studies with a rhesus macaque/SIVsmm9 model. J Acquir Immune Defic Syndr 50:241–249
Dou H, Grotepas CB, McMillan JM, Destache CJ, Chaubal M, Werling J, Kipp J, Rabinow B, Gendelman HE (2009) Macrophage delivery of nanoformulated antiretroviral drug to the brain in a murine model of neuroAIDS. J Immunol 183:661–669
Drzyzga L, Obuchowicz E, Marcinowska A, Herman ZS (2006) Cytokines in schizophrenia and the effects of antipsychotic drugs. Brain Behav Immun 20:532–545
Dunfee R, Thomas ER, Gorry PR, Wang J, Ancuta P, Gabuzda D (2006) Mechanisms of HIV-1 neurotropism. Curr HIV Res 4:267–278
Edgar VA, Sterin-Borda L, Cremaschi GA, Genaro AM (1999) Role of protein kinase C and cAMP in fluoxetine effects on human T-cell proliferation. Eur J Pharmacol 372:65–73
Eigler A, Siegmund B, Emmerich U, Baumann KH, Hartmann G, Endres S (1998) Anti-inflammatory activities of cAMP-elevating agents: enhancement of IL-10 synthesis and concurrent suppression of TNF production. J Leukoc Biol 63:101–107
Eilers M, Roy U, Mondal D (2008) MRP (ABCC) transporters-mediated efflux of anti-HIV drugs, saquinavir and zidovudine, from human endothelial cells. Exp Biol Medicine (Maywood) 233:1149–1160
Familian A, Eikelenboom P, Veerhuis R (2007) Minocycline does not affect amyloid beta phagocytosis by human microglial cells. Neurosci Lett 416:87–91
Fan R, Xu F, Previti ML, Davis J, Grande AM, Robinson JK, Van Nostrand WE (2007) Minocycline reduces microglial activation and improves behavioral deficits in a transgenic model of cerebral microvascular amyloid. J Neurosci 27:3057–3063
Feldman SR, Gottlieb AB, Bala M, Wu Y, Eisenberg D, Guzzo C, Li S, Dooley LT, Menter A (2008) Infliximab improves health-related quality of life in the presence of comorbidities among patients with moderate-to-severe psoriasis. Br J Dermatol 159:704–710
Ferjan I, Erjavec F (1996) Changes in histamine and serotonin secretion from rat peritoneal mast cells caused by antidepressants. Inflamm Res 45:141–144
Fetler L, Amigorena S (2005) Neuroscience. Brain under surveillance: the microglia patrol. Science 309:392–393
Finter NB (1996) The naming of cats—and alpha-interferons. Lancet 348:348–349
Friedman H, Newton C, Klein TW (2003) Microbial infections, immunomodulation, and drugs of abuse. Clin Microbiol Rev 16:209–219
Friedman H, Pross S, Klein TW (2006) Addictive drugs and their relationship with infectious diseases. FEMS Immunol Med Microbiol 47:330–342
Fukui S, Schwarcz R, Rapoport SI, Takada Y, Smith QR (1991) Blood–brain barrier transport of kynurenines: implications for brain synthesis and metabolism. J Neurochem 56:2007–2017
Gao HM, Liu B, Zhang W, Hong JS (2003) Critical role of microglial NADPH oxidase-derived free radicals in the in vitro MPTP model of Parkinson’s disease. FASEB J 17:1954–1956
Gaughran F (2002) Immunity and schizophrenia: autoimmunity, cytokines, and immune responses. Int Rev Neurobiol 52:275–302
Giri RK, Rajagopal V, Kalra VK (2004) Curcumin, the active constituent of turmeric, inhibits amyloid peptide-induced cytochemokine gene expression and CCR5-mediated chemotaxis of THP-1 monocytes by modulating early growth response-1 transcription factor. J Neurochem 91:1199–1210
Glass CK, Saijo K, Winner B, Marchetto MC, Gage FH (2010) Mechanisms underlying inflammation in neurodegeneration. Cell 140:918–934
Golde TE (2006) Disease modifying therapy for AD? J Neurochem 99:689–707
Grant I (2008) Neurocognitive disturbances in HIV. Int Rev Psychiatry 20:33–47
Halassa MM, Haydon PG (2010) Integrated brain circuits: astrocytic networks modulate neuronal activity and behavior. Annu Rev Physiol 72:335–355
Heneka MT, Sastre M, Dumitrescu-Ozimek L, Hanke A, Dewachter I, Kuiperi C, O’Banion K, Klockgether T, Van Leuven F, Landreth GE (2005) Acute treatment with the PPARgamma agonist pioglitazone and ibuprofen reduces glial inflammation and Abeta1-42 levels in APPV717I transgenic mice. Brain 128:1442–1453
Hertz L (2006) Glutamate, a neurotransmitter—and so much more. A synopsis of Wierzba III. Neurochem Int 48:416–425
Hori T, Nakashima T, Take S, Kaizuka Y, Mori T, Katafuchi T (1991) Immune cytokines and regulation of body temperature, food intake and cellular immunity. Brain Res Bull 27:309–313
Huang JT, Welch JS, Ricote M, Binder CJ, Willson TM, Kelly C, Witztum JL, Funk CD, Conrad D, Glass CK (1999) Interleukin-4-dependent production of PPAR-gamma ligands in macrophages by 12/15-lipoxygenase. Nature 400:378–382
int' Veld BA, Ruitenberg A, Hofman A, Launer LJ, van Duijn CM, Stijnen T, Breteler MM, Stricker BH (2001) Nonsteroidal antiinflammatory drugs and the risk of Alzheimer’s disease. N Engl J Med 345:1515–1521
Islam M, Frye RF, Richards TJ, Sbeitan I, Donnelly SS, Glue P, Agarwala SS, Kirkwood JM (2002) Differential effect of IFNalpha-2b on the cytochrome P450 enzyme system: a potential basis of IFN toxicity and its modulation by other drugs. Clin Cancer Res 8:2480–2487
Jantzen PT, Connor KE, DiCarlo G, Wenk GL, Wallace JL, Rojiani AM, Coppola D, Morgan D, Gordon MN (2002) Microglial activation and beta-amyloid deposit reduction caused by a nitric oxide-releasing nonsteroidal anti-inflammatory drug in amyloid precursor protein plus presenilin-1 transgenic mice. J Neurosci 22:2246–2254
Jiang J, Wang W, Sun YJ, Hu M, Li F, Zhu DY (2007) Neuroprotective effect of curcumin on focal cerebral ischemic rats by preventing blood–brain barrier damage. Eur J Pharmacol 561:54–62
Kang G, Kong PJ, Yuh YJ, Lim SY, Yim SV, Chun W, Kim SS (2004) Curcumin suppresses lipopolysaccharide-induced cyclooxygenase-2 expression by inhibiting activator protein 1 and nuclear factor kappab bindings in BV2 microglial cells. J Pharmacol Sci 94:325–328
Kenis G, Maes M (2002) Effects of antidepressants on the production of cytokines. Int J Neuropsychopharmacol 5:401–412
Khairova RA, Machado-Vieira R, Du J, Manji HK (2009) A potential role for pro-inflammatory cytokines in regulating synaptic plasticity in major depressive disorder. Int J Neuropsychopharmacol 12:561–578
Kim YK, Kim L, Lee MS (2000) Relationships between interleukins, neurotransmitters and psychopathology in drug-free male schizophrenics. Schizophr Res 44:165–175
Kim DJ, Kim W, Yoon SJ, Go HJ, Choi BM, Jun TY, Kim YK (2001) Effect of risperidone on serum cytokines. Int J Neurosci 111:11–19
Kim SD, Yang SI, Kim HC, Shin CY, Ko KH (2007) Inhibition of GSK-3beta mediates expression of MMP-9 through ERK1/2 activation and translocation of NF-kappaB in rat primary astrocyte. Brain Res 1186:12–20
Kim J, Lee HJ, Lee KW (2010) Naturally occurring phytochemicals for the prevention of Alzheimer’s disease. J Neurochem 112:1415–1430
Kraft-Terry SD, Buch SJ, Fox HS, Gendelman HE (2009) A coat of many colors: neuroimmune crosstalk in human immunodeficiency virus infection. Neuron 64:133–145
Krishnan R, Cella D, Leonardi C, Papp K, Gottlieb AB, Dunn M, Chiou CF, Patel V, Jahreis A (2007) Effects of etanercept therapy on fatigue and symptoms of depression in subjects treated for moderate to severe plaque psoriasis for up to 96 weeks. Br J Dermatol 157:1275–1277
Kronfol Z, Remick DG (2000) Cytokines and the brain: implications for clinical psychiatry. Am J Psychiatry 157:683–694
Kubera M, Kenis G, Bosmans E, Scharpe S, Maes M (2000) Effects of serotonin and serotonergic agonists and antagonists on the production of interferon-gamma and interleukin-10. Neuropsychopharmacology 23:89–98
Kukar T, Murphy MP, Eriksen JL, Sagi SA, Weggen S, Smith TE, Ladd T, Khan MA, Kache R, Beard J, Dodson M, Merit S, Ozols VV, Anastasiadis PZ, Das P, Fauq A, Koo EH, Golde TE (2005) Diverse compounds mimic Alzheimer disease-causing mutations by augmenting Abeta42 production. Nat Med 11:545–550
Kumar R, Orsoni S, Norman L, Verma AS, Tirado G, Giavedoni LD, Staprans S, Miller GM, Buch SJ, Kumar A (2006) Chronic morphine exposure causes pronounced virus replication in cerebral compartment and accelerated onset of AIDS in SIV/SHIV-infected Indian rhesus macaques. Virology 354:192–206
Letendre SL, Woods SP, Ellis RJ, Atkinson JH, Masliah E, van den Brande G, Durelle J, Grant I, Everall I (2006) Lithium improves HIV-associated neurocognitive impairment. AIDS 20:1885–1888
Letendre S, Marquie-Beck J, Capparelli E, Best B, Clifford D, Collier AC, Gelman BB, McArthur JC, McCutchan JA, Morgello S, Simpson D, Grant I, Ellis RJ (2008) Validation of the CNS penetration-effectiveness rank for quantifying antiretroviral penetration into the central nervous system. Arch Neurol 65:65–70
Lim CS, Jin DQ, Mok H, Oh SJ, Lee JU, Hwang JK, Ha I, Han JS (2005) Antioxidant and antiinflammatory activities of xanthorrhizol in hippocampal neurons and primary cultured microglia. J Neurosci Res 82:831–838
Linnoila M, Whorton AR, Rubinow DR, Cowdry RW, Ninan PT, Waters RN (1983) CSF prostaglandin levels in depressed and schizophrenic patients. Arch Gen Psychiatry 40:405–406
Lipton SA (2004) Paradigm shift in NMDA receptor antagonist drug development: molecular mechanism of uncompetitive inhibition by memantine in the treatment of Alzheimer’s disease and other neurologic disorders. J Alzheimers Dis 6(Suppl):S61–S74
Loftis JM, Hauser P (2004) The phenomenology and treatment of interferon-induced depression. J Affect Disord 82:175–190
Lue LF, Rydel R, Brigham EF, Yang LB, Hampel H, Murphy GM Jr, Brachova L, Yan SD, Walker DG, Shen Y, Rogers J (2001) Inflammatory repertoire of Alzheimer’s disease and nondemented elderly microglia in vitro. Glia 35:72–79
Luna-Medina R, Cortes-Canteli M, Alonso M, Santos A, Martínez A, Perez-Castillo A (2005) Regulation of inflammatory response in neural cells in vitro by thiadiazolidinones derivatives through peroxisome proliferator-activated receptor gamma activation. J Biol Chem 280:21453–21462
Maes M (1995) Evidence for an immune response in major depression: a review and hypothesis. Prog Neuropsychopharmacol Biol Psychiatry 19:11–38
Maes M, Meltzer HY, Bosmans E (1994) Immune-inflammatory markers in schizophrenia: comparison to normal controls and effects of clozapine. Acta Psychiatr Scand 89:346–351
Maes M, Bosmans E, Kenis G, De Jong R, Smith RS, Meltzer HY (1997) In vivo immunomodulatory effects of clozapine in schizophrenia. Schizophr Res 26:221–225
Maes M, Bocchio Chiavetto L, Bignotti S, Battisa Tura GJ, Pioli R, Boin F, Kenis G, Bosmans E, de Jongh R, Altamura CA (2002) Increased serum interleukin-8 and interleukin-10 in schizophrenic patients resistant to treatment with neuroleptics and the stimulatory effects of clozapine on serum leukemia inhibitory factor receptor. Schizophr Res 54:281–291
Malek-Ahmadi P (2001) Mood disorders associated with interferon treatment: theoretical and practical considerations. Ann Pharmacother 35:489–495
Martinez A, Alonso M, Castro A, Pérez C, Moreno FJ (2002) First non-ATP competitive glycogen synthase kinase 3 beta (GSK-3beta) inhibitors: thiadiazolidinones (TDZD) as potential drugs for the treatment of Alzheimer’s disease. J Med Chem 45:1292–1299
Masek K, Slansky J, Petrovicky P, Hadden JW (2003) Neuroendocrine immune interactions in health and disease. Int Immunopharmacol 3:1235–1246
McArthur JC (1987) Neurologic manifestations of AIDS. Medicine (Baltimore) 66:407–437
McArthur JC, Hoover DR, Bacellar H, Miller EN, Cohen BA, Becker JT, Graham NM, McArthur JH, Selnes OA, Jacobson LP et al (1993) Dementia in AIDS patients: incidence and risk factors. Multicenter AIDS Cohort Study. Neurology 43:2245–2252
McGeer PL, McGeer EG (1998) Glial cell reactions in neurodegenerative diseases: pathophysiology and therapeutic interventions. Alzheimer Dis Assoc Disord Suppl 2:S1–S6
McGeer PL, McGeer EG (2007) NSAIDs and Alzheimer disease: epidemiological, animal model and clinical studies. Neurobiol Aging 28:639–647
McGeer PL, Schulzer M, McGeer EG (1996) Arthritis and anti-inflammatory agents as possible protective factors for Alzheimer’s disease: a review of 17 epidemiologic studies. Neurology 47:425–432
Meisner F, Scheller C, Kneitz S, Sopper S, Neuen-Jacob E, Riederer P, ter Meulen V, Koutsilieri E (2008) Memantine upregulates BDNF and prevents dopamine deficits in SIV-infected macaques: a novel pharmacological action of memantine. Neuropsychopharmacology 33:2228–2236
Miller AH (2009) Norman Cousins Lecture. Mechanisms of cytokine-induced behavioral changes: psychoneuroimmunology at the translational interface. Brain Behav Immun 23:149–158
Miller DS, Bauer B, Hartz AM (2008) Modulation of P-glycoprotein at the blood–brain barrier: opportunities to improve central nervous system pharmacotherapy. Pharmacol Rev 60:196–209
Mittleman BB, Castellanos FX, Jacobsen LK, Rapoport JL, Swedo SE, Shearer GM (1997) Cerebrospinal fluid cytokines in pediatric neuropsychiatric disease. J Immunol 159:2994–2999
Miyamoto S, Duncan GE, Marx CE, Lieberman JA (2005) Treatments for schizophrenia: a critical review of pharmacology and mechanisms of action of antipsychotic drugs. Mol Psychiatry 10:79–104
Mogi M, Li JM, Tsukuda K, Iwanami J, Min LJ, Sakata A, Fujita T, Iwai M, Horiuchi M (2008) Telmisartan prevented cognitive decline partly due to PPAR-gamma activation. Biochem Biophys Res Commun 375:446–449
Monteleone P, Fabrazzo M, Tortorella A, Maj M (1997) Plasma levels of interleukin-6 and tumor necrosis factor alpha in chronic schizophrenia: effects of clozapine treatment. Psychiatry Res 71:11–17
Moots RJ, Al-Saffar Z, Hutchinson D, Golding SP, Young SP, Bacon PA, McLaughlin PJ (1999) Old drug, new tricks: haloperidol inhibits secretion of proinflammatory cytokines. Ann Rheum Dis 58:585–587
Muller N, Riedel M, Gruber R, Ackenheil M, Schwarz MJ (2000) The immune system and schizophrenia. An integrative view. Ann NY Acad Sci 917:456–467
Muller N, Riedel M, Scheppach C, Brandstatter B, Sokullu S, Krampe K, Ulmschneider M, Engel RR, Moller HJ, Schwarz MJ (2002) Beneficial antipsychotic effects of celecoxib add-on therapy compared to risperidone alone in schizophrenia. Am J Psychiatry 159:1029–1034
Muller N, Strassnig M, Schwarz MJ, Ulmschneider M, Riedel M (2004) COX-2 inhibitors as adjunctive therapy in schizophrenia. Expert Opin Investig Drugs 13:1033–1044
Muller N, Schwarz MJ, Dehning S, Douhe A, Cerovecki A, Goldstein-Muller B, Spellmann I, Hetzel G, Maino K, Kleindienst N, Moller HJ, Arolt V, Riedel M (2006) The cyclooxygenase-2 inhibitor celecoxib has therapeutic effects in major depression: results of a double-blind, randomized, placebo controlled, add-on pilot study to reboxetine. Mol Psychiatry 11:680–684
Nagy L, Tontonoz P, Alvarez JG, Chen H, Evans RM (1998) Oxidized LDL regulates macrophage gene expression through ligand activation of PPARgamma. Cell 93:229–240
Nair MP, Saiyed ZM, Nair N, Gandhi NH, Rodriguez JW, Boukli N, Provencio-Vasquez E, Malow RM, Miguez-Burbano MJ (2009) Methamphetamine enhances HIV-1 infectivity in monocyte derived dendritic cells. J Neuroimmune Pharmacol 4:129–139
Nath A, Haughey NJ, Jones M, Anderson C, Bell JE, Geiger JD (2000) Synergistic neurotoxicity by human immunodeficiency virus proteins Tat and gp120: protection by memantine. Ann Neurol 47:186–194
Nath A, Schiess N, Venkatesan A, Rumbaugh J, Sacktor N, McArthur J (2008) Evolution of HIV dementia with HIV infection. Int Rev Psychiatry 20:25–31
Nimmerjahn A, Kirchhoff F, Helmchen F (2005) Resting microglial cells are highly dynamic surveillants of brain parenchyma in vivo. Science 308:1314–1318
Norris JG, Benveniste EN (1993) Interleukin-6 production by astrocytes: induction by the neurotransmitter norepinephrine. J Neuroimmunol 45:137–145
Nowacek A, Gendelman HE (2009) NanoART, neuroAIDS and CNS drug delivery. Nanomedicine (Lond) 4:557–574
O'Brien SM, Scott LV, Dinan TG (2004) Cytokines: abnormalities in major depression and implications for pharmacological treatment. Hum Psychopharmacol 19:397–403
O’Brien SM, Scully P, Dinan TG (2008) Increased tumor necrosis factor-alpha concentrations with interleukin-4 concentrations in exacerbations of schizophrenia. Psychiatry Res 160:256–262
Ohishi K, Ueno R, Nishino S, Sakai T, Hayaishi O (1988) Increased level of salivary prostaglandins in patients with major depression. Biol Psychiatry 23:326–334
Opp MR (2005) Cytokines and sleep. Sleep Med Rev 9:355–364
Pae CU, Yoon CH, Kim TS, Kim JJ, Park SH, Lee CU, Lee SJ, Lee C, Paik IH (2006) Antipsychotic treatment may alter T-helper (TH) 2 arm cytokines. Int Immunopharmacol 6:666–671
Park S, Geddes TJ, Javitch JA, Kuhn DM (2003) Dopamine prevents nitration of tyrosine hydroxylase by peroxynitrite and nitrogen dioxide: is nitrotyrosine formation an early step in dopamine neuronal damage? J Biol Chem 278:28736–28742
Petrovsky N (2001) Towards a unified model of neuroendocrine–immune interaction. Immunol Cell Biol 79:350–357
Pollmacher T, Hinze-Selch D, Mullington J (1996) Effects of clozapine on plasma cytokine and soluble cytokine receptor levels. J Clin Psychopharmacol 16:403–409
Pollmacher T, Hinze-Selch D, Fenzel T, Kraus T, Schuld A, Mullington J (1997) Plasma levels of cytokines and soluble cytokine receptors during treatment with haloperidol. Am J Psychiatry 154:1763–1765
Potvin S, Stip E, Sepehry AA, Gendron A, Bah R, Kouassi E (2008) Inflammatory cytokine alterations in schizophrenia: a systematic quantitative review. Biol Psychiatry 63:801–808
Rahman I, Marwick J, Kirkham P (2004) Redox modulation of chromatin remodeling: impact on histone acetylation and deacetylation, NF-kappaB and pro-inflammatory gene expression. Biochem Pharmacol 68:1255–1267
Rainey-Smith SR, Andersson DA, Williams RJ, Rattray M (2010) Tumour necrosis factor alpha induces rapid reduction in AMPA receptor-mediated calcium entry in motor neurones by increasing cell surface expression of the GluR2 subunit: relevance to neurodegeneration. J Neurochem 113:692–703
Ramchand R, Wei J, Ramchand CN, Hemmings GP (1994) Increased serum IgE in schizophrenic patients who responded poorly to neuroleptic treatment. Life Sci 54:1579–1584
Randall RE, Goodbourn S (2008) Interferons and viruses: an interplay between induction, signalling, antiviral responses and virus countermeasures. J Gen Virol 89:1–47
Riedel M, Spellmann I, Schwarz MJ, Strassnig M, Sikorski C, Moller HJ, Muller N (2007) Decreased T cellular immune response in schizophrenic patients. J Psychiatr Res 41:3–7
Rippeth JD, Heaton RK, Carey CL, Marcotte TD, Moore DJ, Gonzalez R, Wolfson T, Grant I (2004) Methamphetamine dependence increases risk of neuropsychological impairment in HIV infected persons. J Int Neuropsychol Soc 10:1–14
Rothermundt M, Arolt V, Bayer TA (2001) Review of immunological and immunopathological findings in schizophrenia. Brain Behav Immun 15:319–339
Roy S, Wang J, Kelschenbach J, Koodie L, Martin J (2006) Modulation of immune function by morphine: implications for susceptibility to infection. J Neuroimmune Pharmacol 1:77–89
Sacre S, Medghalchi M, Gregory B, Brennan F, Williams R (2010) Fluoxetine and citalopram exhibit potent antiinflammatory activity in human and murine models of rheumatoid arthritis and inhibit Toll-like receptors. Arthritis Rheum 62:683–693
Saper CB, Breder CD (1994) The neurologic basis of fever. N Engl J Med 330:1880–1886
Sawada M, Suzumura A, Marunouchi T (1995) Cytokine network in the central nervous system and its roles in growth and differentiation of glial and neuronal cells. Int J Dev Neurosci 13:253–264
Scher JU, Pillinger MH (2009) The anti-inflammatory effects of prostaglandins. J Investig Med 57:703–708
Schifitto G, Peterson DR, Zhong J, Ni H, Cruttenden K, Gaugh M, Gendelman HE, Boska M, Gelbard H (2006) Valproic acid adjunctive therapy for HIV-associated cognitive impairment: a first report. Neurology 66:919–921
Schifitto G, Navia BA, Yiannoutsos CT, Marra CM, Chang L, Ernst T, Jarvik JG, Miller EN, Singer EJ, Ellis RJ, Kolson DL, Simpson D, Nath A, Berger J, Shriver SL, Millar LL, Colquhoun D, Lenkinski R, Gonzalez RG, Lipton SA (2007) Memantine and HIV-associated cognitive impairment: a neuropsychological and proton magnetic resonance spectroscopy study. AIDS 21:1877–1886
Schousboe A (2003) Role of astrocytes in the maintenance and modulation of glutamatergic and GABAergic neurotransmission. Neurochem Res 28:347–352
Schousboe A, Sarup A, Bak LK, Waagepetersen HS, Larsson OM (2004) Role of astrocytic transport processes in glutamatergic and GABAergic neurotransmission. Neurochem Int 45:521–527
Schuld A, Kraus T, Haack M, Hinze-Selch D, Kuhn M, Pollmacher T (2000) Plasma levels of cytokines and soluble cytokine receptors during treatment with olanzapine. Schizophr Res 43:164–166
Schwarcz R, Whetsell WO Jr, Mangano RM (1983) Quinolinic acid: an endogenous metabolite that produces axon-sparing lesions in rat brain. Science 219:316–318
Selkoe DJ (2001) Alzheimer’s disease: genes, proteins, and therapy. Physiol Rev 81:741–766
Shen Y, Connor TJ, Nolan Y, Kelly JP, Leonard BE (1999) Differential effect of chronic antidepressant treatments on lipopolysaccharide-induced depressive-like behavioural symptoms in the rat. Life Sci 65:1773–1786
Shie FS, Woltjer RL (2007) Manipulation of microglial activation as a therapeutic strategy in Alzheimer’s disease. Curr Med Chem 14:2865–2871
Sleijfer S, Bannink M, Van Gool AR, Kruit WH, Stoter G (2005) Side effects of interferon-alpha therapy. Pharm World Sci 27:423–431
Song C, Lin A, Bonaccorso S, Heide C, Verkerk R, Kenis G, Bosmans E, Scharpe S, Whelan A, Cosyns P, de Jongh R, Maes M (1998) The inflammatory response system and the availability of plasma tryptophan in patients with primary sleep disorders and major depression. J Affect Disord 49:211–219
Speciale C, Hares K, Schwarcz R, Brookes N (1989) High-affinity uptake of l-kynurenine by a Na+-independent transporter of neutral amino acids in astrocytes. J Neurosci 9:2066–2072
Stolina M, Sharma S, Lin Y, Dohadwala M, Gardner B, Luo J, Zhu L, Kronenberg M, Miller PW, Portanova J, Lee JC, Dubinett SM (2000) Specific inhibition of cyclooxygenase 2 restores antitumor reactivity by altering the balance of IL-10 and IL-12 synthesis. J Immunol 164:361–370
Struzyńska LA (2009) Glutamatergic component of lead toxicity in adult brain: the role of astrocytic glutamate transporters. Neurochem Int 55:151–156
Szabo G (1997) Alcohol’s contribution to compromised immunity. Alcohol Health Res World 21:30–41
Szelenyi J (2001) Cytokines and the central nervous system. Brain Res Bull 54:329–338
Taler M, Gil-Ad I, Lomnitski L, Korov I, Baharav E, Bar M, Zolokov A, Weizman A (2007) Immunomodulatory effect of selective serotonin reuptake inhibitors (SSRIs) on human T lymphocyte function and gene expression. Eur Neuropsychopharmacol 17:774–780
Taler M, Bar M, Korob I, Lomnitski L, Baharav E, Grunbaum-Novak N, Weizman A, Gil-Ad I (2008) Evidence for an inhibitory immunomodulatory effect of selected antidepressants on rat splenocytes: possible relevance to depression and hyperactive-immune disorders. Int Immunopharmacol 8:526–533
Taylor DL, Jones F, Kubota ES, Pocock JM (2005) Stimulation of microglial metabotropic glutamate receptor mGlu2 triggers tumor necrosis factor alpha-induced neurotoxicity in concert with microglial-derived Fas ligand. J Neurosci 25:2952–2964
Thadani PV, Sharp C (1994) Drugs of abuse and dysfunction of neuroendocrine and immune systems: the importance of animal research. J Addict Dis 13:1–8
Turnbull AV, Rivier C (1995) Regulation of the HPA axis by cytokines. Brain Behav Immun 9:253–275
Tyring S, Gottlieb A, Papp K, Gordon K, Leonardi C, Wang A, Lalla D, Woolley M, Jahreis A, Zitnik R, Cella D, Krishnan R (2006) Etanercept and clinical outcomes, fatigue, and depression in psoriasis: double-blind placebo-controlled randomised phase III trial. Lancet 367:29–35
Tzingounis AV, Wadiche JI (2007) Glutamate transporters: confining runaway excitation by shaping synaptic transmission. Nat Rev Neurosci 8:935–947
Urbina A, Jones K (2004) Crystal methamphetamine, its analogues, and HIV infection: medical and psychiatric aspects of a new epidemic. Clin Infect Dis 38:890–894
Varatharajan L, Thomas SA (2009) The transport of anti-HIV drugs across blood–CNS interfaces: summary of current knowledge and recommendations for further research. Antiviral Res 82:A99–A109
Vitkovic L, Bockaert J, Jacque C (2000) “Inflammatory”cytokines: neuromodulators in normal brain? J Neurochem 74:457–471
Wichers MC, Maes M (2004) The role of indoleamine 2,3-dioxygenase (IDO) in the pathophysiology of interferon-alpha-induced depression. J Psychiatry Neurosci 29:11–17
Wilson DR, Warise L (2008) Cytokines and their role in depression. Perspect Psychiatr Care 44:285–289
Wojtera M, Sikorska B, Sobow T, Liberski PP (2005) Microglial cells in neurodegenerative disorders. Folia Neuropathol 43:311–321
Xia Z, DePierre JW, Nassberger L (1996) Tricyclic antidepressants inhibit IL-6, IL-1 beta and TNF-alpha release in human blood monocytes and IL-2 and interferon-gamma in T cells. Immunopharmacology 34:27–37
Yadav A, Collman RG (2009) CNS inflammation and macrophage/microglial biology associated with HIV-1 infection. J Neuroimmune Pharmacol 4:430–447
Yang F, Lim GP, Begum AN, Ubeda OJ, Simmons MR, Ambegaokar SS, Chen PP, Kayed R, Glabe CG, Frautschy SA, Cole GM (2005) Curcumin inhibits formation of amyloid beta oligomers and fibrils, binds plaques, and reduces amyloid in vivo. J Biol Chem 280:5892–5901
Zhang L, Looney D, Taub D, Chang SL, Way D, Witte MH, Graves MC, Fiala M (1998) Cocaine opens the blood–brain barrier to HIV-1 invasion. J Neurovirol 4:619–626
Zhang XY, Zhou DF, Cao LY, Zhang PY, Wu GY, Shen YC (2004) Changes in serum interleukin-2, -6, and -8 levels before and during treatment with risperidone and haloperidol: relationship to outcome in schizophrenia. J Clin Psychiatry 65:940–947
Zheng J, Gendelman HE (1997) The HIV-1 associated dementia complex: a metabolic encephalopathy fueled by viral replication in mononuclear phagocytes. Curr Opin Neurol 10:319–325
Zink MC, Uhrlaub J, DeWitt J, Voelker T, Bullock B, Mankowski J, Tarwater P, Clements J, Barber S (2005) Neuroprotective and anti-human immunodeficiency virus activity of minocycline. JAMA 293:2003–2011
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FS Shie and YH Chen are the first authors with equal contribution.
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Shie, FS., Chen, YH., Chen, CH. et al. Neuroimmune Pharmacology of Neurodegenerative and Mental Diseases. J Neuroimmune Pharmacol 6, 28–40 (2011). https://doi.org/10.1007/s11481-010-9241-8
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DOI: https://doi.org/10.1007/s11481-010-9241-8