A Systematic Analysis of the Peripheral and CNS Effects of Systemic LPS, IL-1Β, TNF-α and IL-6 Challenges in C57BL/6 Mice

PLoS ONE

Volumn 8, Issue 7, 2013, Pages

  Skelly, Donal T ^a   Hennessy, Edel ^a   Dansereau, Marc Andre ^a   Cunningham, Colm ^a  

^a TRINITY COLLEGE DUBLIN   (Ireland)

Author keywords

[No Author keywords available]

Indexed keywords

CXCL1 CHEMOKINE; CYCLOOXYGENASE 2; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INTERLEUKIN 1BETA; INTERLEUKIN 6; LIPOPOLYSACCHARIDE; MESSENGER RNA; MONOCYTE CHEMOTACTIC PROTEIN 1; PENTRAXIN 3; PROTEIN C FOS; SYNAPTOTAGMIN I; TUMOR NECROSIS FACTOR ALPHA;

ACUTE PHASE RESPONSE; AMYGDALOID NUCLEUS; ANIMAL EXPERIMENT; ARTICLE; BRAIN BLOOD VESSEL; BRAIN LEVEL; C57BL 6 MOUSE; CELL NUCLEUS; CENTRAL NERVOUS SYSTEM; CONTROLLED STUDY; CORE TEMPERATURE; FEMALE; HIPPOCAMPUS; HYPOTHALAMUS; HYPOTHERMIA; IMMUNOHISTOCHEMISTRY; LIVER; LOCOMOTION; MOUSE; NERVOUS SYSTEM INFLAMMATION; NONHUMAN; OPEN FIELD TEST; PERIPHERAL NERVOUS SYSTEM; PROTEIN BLOOD LEVEL; PROTEIN EXPRESSION; PROTEIN LOCALIZATION; PROVOCATION TEST;

ANIMALS; BODY TEMPERATURE; BRAIN; CYTOKINES; FEMALE; GENE EXPRESSION REGULATION; INFLAMMATION; INTERLEUKIN-1BETA; INTERLEUKIN-6; LIPOPOLYSACCHARIDES; LIVER; MICE; MICE, INBRED C57BL; MOTOR ACTIVITY; RNA, MESSENGER; TRANSCRIPTIONAL ACTIVATION; TUMOR NECROSIS FACTOR-ALPHA;

MUS;

EID: 84879708787     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0069123     Document Type: Article

References (124)

1. Steinman L, (2004) Elaborate interactions between the immune and nervous systems. Nat Immunol 5: 575-581. doi:10.1038/ni1078. PubMed: 15164017.
2. Konsman JP, Parnet P, Dantzer R, (2002) Cytokine-induced sickness behaviour: mechanisms and implications. Trends Neurosci 25: 154-159. doi:10.1016/S0166-2236(00)02088-9. PubMed: 11852148.
3. Dantzer R, O'Connor JC, Freund GG, Johnson RW, Kelley KW, (2008) From inflammation to sickness and depression: when the immune system subjugates the brain. Nat Rev Neurosci 9: 46-56. doi:10.1038/nrn2297. PubMed: 18073775.
4. Dantzer R, (2004) Cytokine-induced sickness behaviour: a neuroimmune response to activation of innate immunity. Eur J Pharmacol 500: 399-411. doi:10.1016/j.ejphar.2004.07.040. PubMed: 15464048.
5. Dantzer R, (2001) Cytokine-induced sickness behavior: where do we stand? Brain Behav Immun 15: 7-24. doi:10.1006/brbi.2000.0613. PubMed: 11259077.
6. Dantzer R, (2009) Cytokine, Sickness Behavior, and Depression 29. Immunology and Allergy Clinics of North America. pp.: 247-264.
7. Inui A, (2001) Cytokines and sickness behavior: implications from knockout animal models. Trends Immunol 22: 469-473. doi:10.1016/S1471-4906(01)01981-0. PubMed: 11525927.
8. Wang J, Ando T, Dunn AJ, (1997) Effect of homologous interleukin-1, interleukin-6 and tumor necrosis factor-alpha on the core body temperature of mice. Neuroimmunomodulation 4: 230-236. PubMed: 9650815.
9. Swiergiel AH, Dunn AJ, (1999) The roles of IL-1, IL-6, and TNFalpha in the feeding responses to endotoxin and influenza virus infection in mice. Brain Behav Immun 13: 252-265. doi:10.1006/brbi.1999.0565. PubMed: 10469526.
10. Marsland AL, Gianaros PJ, Abramowitch SM, Manuck SB, Hariri AR, (2008) Interleukin-6 covaries inversely with hippocampal grey matter volume in middle-aged adults. Biol Psychiatry 64: 484-490. doi:10.1016/j.biopsych.2008.04.016. PubMed: 18514163.
11. Yaffe K, Lindquist K, Penninx BW, Simonsick EM, Pahor M, et al. (2003) Inflammatory markers and cognition in well-functioning African-American and white elders. Neurology 61: 76-80. doi:10.1212/01.WNL.0000073620.42047.D7. PubMed: 12847160.
12. Luterman JD, Haroutunian V, Yemul S, Ho L, Purohit D, et al. (2000) Cytokine gene expression as a function of the clinical progression of Alzheimer disease dementia. Arch Neurol 57: 1153-1160. doi:10.1001/archneur.57.8.1153. PubMed: 10927795.
13. Yaffe K, Kanaya A, Lindquist K, Simonsick EM, Harris T, et al. (2004) The metabolic syndrome, inflammation, and risk of cognitive decline. JAMA 292: 2237-2242. doi:10.1001/jama.292.18.2237. PubMed: 15536110.
14. Miller AH, Maletic V, Raison CL, (2009) Inflammation and Its Discontents: The Role of Cytokines in the Pathophysiology of Major Depression. Biol Psychiatry 65: 732-741. doi:10.1016/j.biopsych.2008.11.029. PubMed: 19150053.
15. Dowlati Y, Herrmann N, Swardfager W, Liu H, Sham L, et al. (2010) A meta-analysis of cytokines in major depression. Biol Psychiatry 67: 446-457. doi:10.1016/j.biopsych.2009.09.033. PubMed: 20015486.
16. Tan ZS, Beiser AS, Vasan RS, Roubenoff R, Dinarello CA, et al. (2007) Inflammatory markers and the risk of Alzheimer disease. Neurology 68: 1902-1908. doi:10.1212/01.wnl.0000263217.36439.da. PubMed: 17536046.
17. Swardfager W, Lanctôt K, Rothenburg L, Wong A, Cappell J, et al. (2010) A Meta-Analysis of Cytokines in Alzheimer's Disease. Biol Psychiatry 68: 930-941. doi:10.1016/j.biopsych.2010.06.012. PubMed: 20692646.
18. Chen H, O'Reilly EJ, Schwarzschild MA, Ascherio A, (2008) Peripheral Inflammatory Biomarkers and Risk of Parkinson's Disease. Am J Epidemiol 167: 90-95. PubMed: 17890755.
19. Holmes C, Cunningham C, Zotova E, Woolford J, Dean C, et al. (2009) Systemic inflammation and disease progression in Alzheimer disease. Neurology 73: 768-774. doi:10.1212/WNL.0b013e3181b6bb95. PubMed: 19738171.
20. Beloosesky Y, Hendel D, Weiss A, Hershkovitz A, Grinblat J, et al. (2007) Cytokines and C-reactive protein production in hip-fracture-operated elderly patients. J Gerontol A Biol Sci Med Sci 62: 420-426. doi:10.1093/gerona/62.4.420. PubMed: 17452737.
21. de Rooij SE, van Munster BC, Korevaar JC, Levi M, (2007) Cytokines and acute phase response in delirium. J Psychosom Res 62: 521-525. doi:10.1016/j.jpsychores.2006.11.013. PubMed: 17467406.
22. van Munster BC, Korevaar JC, Zwinderman AH, Levi M, Wiersinga WJ, et al. (2008) Time-course of cytokines during delirium in elderly patients with hip fractures. J Am Geriatr Soc 56: 1704-1709. doi:10.1111/j.1532-5415.2008.01851.x. PubMed: 18691278.
23. MacLullich AM, Edelshain BT, Hall RJ, de Vries A, Howie SE, et al. (2011) Cerebrospinal Fluid Interleukin-8 Levels Are Higher in People with Hip Fracture with Perioperative Delirium Than in Controls. J Am Geriatr Soc 59: 1151-1153. doi:10.1111/j.1532-5415.2011.03428.x. PubMed: 21668926.
24. Godbout JP, Moreau M, Lestage J, Chen J, Sparkman NL, et al. (2008) Aging exacerbates depressive-like behavior in mice in response to activation of the peripheral innate immune system. Neuropsychopharmacology 33: 2341-2351. doi:10.1038/sj.npp.1301649. PubMed: 18075491.
25. O'Connor JC, Lawson MA, Andre C, Moreau M, Lestage J, et al. (2009) Lipopolysaccharide-induced depressive-like behavior is mediated by indoleamine 2,3-dioxygenase activation in mice. Mol Psychiatry 14: 511-522. doi:10.1038/sj.mp.4002148. PubMed: 18195714.
26. Field RH, Gossen A, Cunningham C, (2012) Prior pathology in the basal forebrain cholinergic system predisposes to inflammation induced working memory deficits: reconciling inflammatory and cholinergic hypotheses of delirium. J Neurosci 32: 6288-6294. doi:10.1523/JNEUROSCI.4673-11.2012. PubMed: 22553034.
27. Cunningham C, (2013) Microglia and neurodegeneration: The role of systemic inflammation. Glia 61: 71-90. doi:10.1002/glia.22350. PubMed: 22674585.
28. Murray C, Sanderson DJ, Barkus C, Deacon RM, Rawlins JN, et al. (2012) Systemic inflammation induces acute working memory deficits in the primed brain: relevance for delirium. Neurobiol Aging 33: 603-616 e603.
29. Murray CL, Skelly DT, Cunningham C, (2011) Exacerbation of CNS inflammation and neurodegeneration by systemic LPS treatment is independent of circulating IL-1beta and IL-6. J Neuroinflammation 8: 50. doi:10.1186/1742-2094-8-50. PubMed: 21586125.
30. Field R, Campion S, Warren C, Murray C, Cunningham C, (2010) Systemic challenge with the TLR3 agonist poly I:C induces amplified IFNalpha/beta and IL-1beta responses in the diseased brain and exacerbates chronic neurodegeneration. Brain Behav Immun 24: 996-1007. doi:10.1016/j.bbi.2010.04.004. PubMed: 20399848.
31. Chen L-C, Chen C-C, Liang Y, Tsang N-M, Chang Y-S, et al. (2011) A novel role for TNFAIP2: its correlation with invasion and metastasis in nasopharyngeal carcinoma. Mod Pathol 24: 175-184. doi:10.1038/modpathol.2010.193. PubMed: 21057457.
32. Cunningham O, Campion S, Perry VH, Murray C, Sidenius N, et al. (2009) Microglia and the urokinase plasminogen activator receptor/uPA system in innate brain inflammation. Glia 57: 1802-1814. doi:10.1002/glia.20892. PubMed: 19459212.
33. Koj A, (1996) Initiation of acute phase response and synthesis of cytokines. Biochim Biophys Acta 1317: 84-94. doi:10.1016/S0925-4439(96)00048-8. PubMed: 8950192.
34. Perry VH, Cunningham C, Holmes C, (2007) Systemic infections and inflammation affect chronic neurodegeneration. Nat Rev Immunol 7: 161-167. doi:10.1038/nri2015. PubMed: 17220915.
35. Cunningham C, Campion S, Lunnon K, Murray CL, Woods JF, et al. (2009) Systemic inflammation induces acute behavioral and cognitive changes and accelerates neurodegenerative disease. Biol Psychiatry 65: 304-312. doi:10.1016/j.biopsych.2008.07.024. PubMed: 18801476.
36. Church LD, Cook GP, McDermott MF, (2008) Primer: inflammasomes and interleukin 1beta in inflammatory disorders. Nat Clin Pract Rheumatol 4: 34-42. doi:10.1038/ncpneuro0683. PubMed: 18172447.
37. Marinkovic S, Jahreis GP, Wong GG, Baumann H, (1989) IL-6 modulates the synthesis of a specific set of acute phase plasma proteins in vivo. J Immunol 142: 808-812. PubMed: 2464026.
38. Wang J, Dunn AJ, (1998) Mouse interleukin-6 stimulates the HPA axis and increases brain tryptophan and serotonin metabolism. Neurochem Int 33: 143-154. doi:10.1016/S0197-0186(98)00016-3. PubMed: 9761458.
39. Harden LM, du Plessis I, Roth J, Loram LC, Poole S, et al. (2011) Differences in the relative involvement of peripherally released interleukin (IL)-6, brain IL-1β and prostanoids in mediating lipopolysaccharide-induced fever and sickness behavior. Psychoneuroendocrinology 36: 608-622. doi:10.1016/j.psyneuen.2010.09.003. PubMed: 20926198.
40. Harden LM, du Plessis I, Poole S, Laburn HP, (2006) Interleukin-6 and leptin mediate lipopolysaccharide-induced fever and sickness behavior. Physiol Behav 89: 146-155. doi:10.1016/j.physbeh.2006.05.016. PubMed: 16842830.
41. Nilsberth C, Elander L, Hamzic N, Norell M, Lonn J, et al. (2009) The role of interleukin-6 in lipopolysaccharide-induced fever by mechanisms independent of prostaglandin E2. Endocrinology 150: 1850-1860. doi:10.1210/en.2008-0806. PubMed: 19022895.
42. Lacroix S, Rivest S, (1998) Effect of acute systemic inflammatory response and cytokines on the transcription of the genes encoding cyclooxygenase enzymes (COX-1 and COX-2) in the rat brain. J Neurochem 70: 452-466. PubMed: 9453538.
43. Laflamme N, Rivest S, (1999) Effects of systemic immunogenic insults and circulating proinflammatory cytokines on the transcription of the inhibitory factor kappaB alpha within specific cellular populations of the rat brain. J Neurochem 73: 309-321. PubMed: 10386984.
44. Rivest S, (2001) How circulating cytokines trigger the neural circuits that control the hypothalamic-pituitary-adrenal axis. Psychoneuroendocrinology 26: 761-788. doi:10.1016/S0306-4530(01)00064-6. PubMed: 11585678.
45. Ceciliani F, Giordano A, Spagnolo V, (2002) The systemic reaction during inflammation: the acute-phase proteins. Protein Pept Lett 9: 211-223. doi:10.2174/0929866023408779. PubMed: 12144517.
46. Fong Y, Tracey KJ, Moldawer LL, Hesse DG, Manogue KB, et al. (1989) Antibodies to cachectin/tumor necrosis factor reduce interleukin 1beta and interleukin 6 appearance during lethal bacteremia. J Exp Med 170: 1627-1633. doi:10.1084/jem.170.5.1627. PubMed: 2809510.
47. Fantuzzi G, Dinarello C, (1996) The inflammatory response in interleukin-1beta-deficient mice: comparison with other cytokine-related knock-out mice. J Leukoc Biol 59: 489-493. PubMed: 8613694.
48. Granowitz EV, Porat R, Mier JW, Orencole SF, Callahan MV, et al. (1993) Hematologic and immunomodulatory effects of an interleukin-1 receptor antagonist coinfusion during low-dose endotoxemia in healthy humans. Blood 82: 2985-2990. PubMed: 8219190.
49. Saper CB, Romanovsky AA, Scammell TE, (2012) Neural circuitry engaged by prostaglandins during the sickness syndrome. Nat Neurosci 15: 1088-1095. doi:10.1038/nn.3159. PubMed: 22837039.
50. Teeling JL, Cunningham C, Newman TA, Perry VH, (2010) The effect of non-steroidal anti-inflammatory agents on behavioural changes and cytokine production following systemic inflammation: Implications for a role of COX-1. Brain Behav Immun 24: 409-419. doi:10.1016/j.bbi.2009.11.006. PubMed: 19931610.
51. Nadjar A, Combe C, Laye S, Tridon V, Dantzer R, et al. (2003) Nuclear factor kappa B nuclear translocation as a crucial marker of brain response to interleukin-1. A study in rat and interleukin-1 type I deficient mouse. J Neurochem 87: 1024-1036. PubMed: 14622131.
52. Gosselin D, Rivest S, (2007) Role of IL-1 and TNF in the brain: Twenty years of progress on a Dr. Jekyll/Mr. Hyde duality of the innate immune system. Brain Behav Immun 21: 281-289. doi:10.1016/j.bbi.2006.12.004. PubMed: 17275255.
53. Zhang J, Rivest S, (2003) Is survival possible without arachidonate metabolites in the brain during systemic infection? News Physiol Sci 18: 137-142. PubMed: 12869612.
54. Turrin NP, Rivest S, (2004) Unraveling the molecular details involved in the intimate link between the immune and neuroendocrine systems. Exp Biol Med (Maywood) 229: 996-1006.
55. Nadjar A, Bluthe RM, May MJ, Dantzer R, Parnet P, (2005) Inactivation of the cerebral NFkappaB pathway inhibits interleukin-1beta-induced sickness behavior and c-Fos expression in various brain nuclei. Neuropsychopharmacology 30: 1492-1499. doi:10.1038/sj.npp.1300755. PubMed: 15900319.
56. Balsara RD, Merryman R, Virjee F, Northway C, Castellino FJ, et al. (2011) A deficiency of uPAR alters endothelial angiogenic function and cell morphology. Vasc Cell. p. pp. 3: 10.
57. Margheri F, Chilla A, Laurenzana A, Serrati S, Mazzanti B, et al. (2011) Endothelial progenitor cell-dependent angiogenesis requires localization of the full-length form of uPAR in caveolae. Blood 118: 3743-3755. doi:10.1182/blood-2011-02-338681. PubMed: 21803847.
58. Stach K, Nguyen XD, Lang S, Elmas E, Weiss C, et al. (2012) Simvastatin and atorvastatin attenuate VCAM-1 and uPAR expression on human endothelial cells and platelet surface expression of CD40 ligand. Cardiol J 19: 20-28. doi:10.5603/CJ.2012.0005. PubMed: 22298164.
59. Gosselin D, Rivest S, (2008) MyD88 signaling in brain endothelial cells is essential for the neuronal activity and glucocorticoid release during systemic inflammation. Mol Psychiatry 13: 480-497. doi:10.1038/sj.mp.4002122. PubMed: 18180766.
60. Goehler L, Gaykema R, Hammack S, Maier S, Watkins L, (1998) Interleukin-1 induces c-Fos immunoreactivity in primary afferent neurons of the vagus nerve. Brain Res 804: 306-310. doi:10.1016/S0006-8993(98)00685-4. PubMed: 9757071.
61. Konsman JP, Luheshi GN, Bluthe RM, Dantzer R, (2000) The vagus nerve mediates behavioural depression, but not fever, in response to peripheral immune signals; a functional anatomical analysis. Eur J Neurosci 12: 4434-4446. doi:10.1046/j.0953-816X.2000.01319.x. PubMed: 11122354.
62. Chakravarty S, Herkenham M, (2005) Toll-like receptor 4 on nonhematopoietic cells sustains CNS inflammation during endotoxemia, independent of systemic cytokines. J Neurosci 25: 1788-1796. doi:10.1523/JNEUROSCI.4268-04.2005. PubMed: 15716415.
63. Cunningham C, Maclullich AM, (2013) At the extreme end of the psychoneuroimmunological spectrum: delirium as a maladaptive sickness behaviour response. Brain Behav Immun 28: 1-13. doi:10.1016/j.bbi.2012.07.012. PubMed: 22884900.
64. Clark K, Plater L, Peggie M, Cohen P, (2009) Use of the Pharmacological Inhibitor BX795 to Study the Regulation and Physiological Roles of TBK1 and IκB Kinase ε{lunate}. J Biol Chem 284: 14136-14146. doi:10.1074/jbc.M109.000414. PubMed: 19307177.
65. Clark K, Peggie M, Plater L, Sorcek RJ, Young ER, et al. (2011) Novel cross-talk within the IKK family controls innate immunity. Biochem J 434: 93-104. doi:10.1042/BJ20101701. PubMed: 21138416.
66. Colonna M, (2007) TLR pathways and IFN-regulatory factors: to each its own. Eur J Immunol 37: 306-309. doi:10.1002/eji.200637009. PubMed: 17273997.
67. Kawai T, Takeuchi O, Fujita T, Inoue J-i, Mühlradt PF, et al. (2001) Lipopolysaccharide Stimulates the MyD88-Independent Pathway and Results in Activation of IFN-Regulatory Factor 3 and the Expression of a Subset of Lipopolysaccharide-Inducible Genes. J Immunol 167: 5887-5894. PubMed: 11698465.
68. Osera C, Pascale A, Amadio M, Venturini L, Govoni S, et al. (2011) Pentraxins and Alzheimer's disease: At the interface between biomarkers and pharmacological targets. Ageing Res Rev.
69. Ko C-Y, Chang L-H, Lee Y-C, Sterneck E, Cheng C-P, et al. (2012) CCAAT/enhancer binding protein delta (CEBPD) elevating PTX3 expression inhibits macrophage-mediated phagocytosis of dying neuron cells. Neurobiology of Aging 33: 422.e411-422.e425.
70. Hughes MM, Field RH, Perry VH, Murray CL, Cunningham C, (2010) Microglia in the degenerating brain are capable of phagocytosis of beads and of apoptotic cells, but do not efficiently remove PrPSc, even upon LPS stimulation. Glia 58: 2017-2030. doi:10.1002/glia.21070. PubMed: 20878768.
71. Bell MD, Taub DD, Perry VH, (1996) Overriding the brain's intrinsic resistance to leukocyte recruitment with intraparenchymal injections of recombinant chemokines. Neuroscience 74: 283-292. doi:10.1016/0306-4522(96)00083-8. PubMed: 8843093.
72. Anthony D, Dempster R, Fearn S, Clements J, Wells G, et al. (1998) CXC chemokines generate age-related increases in neutrophil-mediated brain inflammation and blood-brain barrier breakdown. Curr Biol 8: 923-926. doi:10.1016/S0960-9822(07)00373-9. PubMed: 9707404.
73. Dzenko K, Song L, Ge S, Kuziel W, Pachter J, (2005) CCR2 expression by brain microvascular endothelial cells is critical for macrophage transendothelial migration in response to CCL2. Microvasc Res 70: 53-64. doi:10.1016/j.mvr.2005.04.005. PubMed: 15927208.
74. Echeverry S, Shi X, Rivest S, Zhang J, (2011) Peripheral nerve injury alters blood-spinal cord barrier functional and molecular integrity through a selective inflammatory pathway. J Neurosci Off J Soc Neurosci 31: 10819-10828. doi:10.1523/JNEUROSCI.1642-11.2011.
75. Stamatovic S, Keep R, Kunkel S, Andjelkovic A, (2003) Potential role of MCP-1 in endothelial cell tight junction 'opening': signaling via Rho and Rho kinase. J Cell Sci 116: 4615-4628. doi:10.1242/jcs.00755. PubMed: 14576355.
76. Adler M, Rogers T, (2005) Are chemokines the third major system in the brain? J Leukoc Biol 78: 1204-1209. doi:10.1189/jlb.0405222. PubMed: 16204637.
77. Rostène W, Dansereau M-A, Godefroy D, Van Steenwinckel J, Reaux-Le Goazigo A, et al. (2011) Neurochemokines: a menage a trois providing new insights on the functions of chemokines in the central nervous system. J Neurochem 118: 680-694. doi:10.1111/j.1471-4159.2011.07371.x. PubMed: 21722132.
78. Banisadr G, Gosselin R-D, Mechighel P, Kitabgi P, Rostène W, et al. (2005) Highly regionalized neuronal expression of monocyte chemoattractant protein-1 (MCP-1/CCL2) in rat brain: evidence for its colocalization with neurotransmitters and neuropeptides. J Comp Neurol 489: 275-292. doi:10.1002/cne.20598. PubMed: 16025454.
79. Conductier G, Blondeau N, Guyon A, Nahon J-L, Rovère C, (2010) The role of monocyte chemoattractant protein MCP1/CCL2 in neuroinflammatory diseases. J Neuroimmunol 224: 93-100. doi:10.1016/j.jneuroim.2010.05.010. PubMed: 20681057.
80. Vallès A, Grijpink-Ongering L, de Bree F, Tuinstra T, Ronken E, (2006) Differential regulation of the CXCR2 chemokine network in rat brain trauma: implications for neuroimmune interactions and neuronal survival. Neurobiol Dis 22: 312-322. doi:10.1016/j.nbd.2005.11.015. PubMed: 16472549.
81. Cho J, Gruol D, (2008) The chemokine CCL2 activates p38 mitogen-activated protein kinase pathway in cultured rat hippocampal cells. J Neuroimmunol 199: 94-103. doi:10.1016/j.jneuroim.2008.05.011. PubMed: 18584881.
82. Nelson T, Hao C, Manos J, Ransohoff R, Gruol D, (2011) Altered hippocampal synaptic transmission in transgenic mice with astrocyte-targeted enhanced CCL2 expression. Brain Behav Immun 25 (Suppl 1):: 19.
83. Zhou Y, Tang H, Liu J, Dong J, Xiong H, (2011) Chemokine CCL2 modulation of neuronal excitability and synaptic transmission in rat hippocampal slices. J Neurochem 116: 406-414. doi:10.1111/j.1471-4159.2010.07121.x. PubMed: 21105875.
84. Campbell SJ, Meier U, Mardiguian S, Jiang Y, Littleton ET, et al. (2010) Sickness behaviour is induced by a peripheral CXC-chemokine also expressed in multiple sclerosis and EAE. Brain Behav Immun 24: 738-746. doi:10.1016/j.bbi.2010.01.011. PubMed: 20138139.
85. Giovannelli A, Limatola C, Ragozzino D, Mileo A, Ruggieri A, et al. (1998) CXC chemokines interleukin-8 (IL-8) and growth-related gene product alpha (GROalpha) modulate Purkinje neuron activity in mouse cerebellum. J Neuroimmunol 92: 122-132. doi:10.1016/S0165-5728(98)00192-1. PubMed: 9916887.
86. Xia M, Hyman B, (2002) GROalpha/KC, a chemokine receptor CXCR2 ligand, can be a potent trigger for neuronal ERK1/2 and PI-3 kinase pathways and for tau hyperphosphorylation-a role in Alzheimer's disease? J Neuroimmunol 122: 55-64. doi:10.1016/S0165-5728(01)00463-5. PubMed: 11777543.
87. Puma C, Danik M, Quirion R, Ramon F, Williams S, (2001) The chemokine interleukin-8 acutely reduces Ca(2+) currents in identified cholinergic septal neurons expressing CXCR1 and CXCR2 receptor mRNAs. J Neurochem 78: 960-971. doi:10.1046/j.1471-4159.2001.00469.x. PubMed: 11553670.
88. Watson K, Fan GH, (2005) Macrophage inflammatory protein 2 inhibits beta-amyloid peptide (1-42)-mediated hippocampal neuronal apoptosis through activation of mitogen-activated protein kinase and phosphatidylinositol 3-kinase signaling pathways. Mol Pharmacol 67: 757-765. PubMed: 15608143.
89. De Paola M, Buanne P, Biordi L, Bertini R, Ghezzi P, et al. (2007) Chemokine MIP-2/CXCL2, acting on CXCR2, induces motor neuron death in primary cultures. Neuroimmunomodulation 14: 310-316. doi:10.1159/000123834. PubMed: 18391506.
90. Schröder J, Kahlke V, Staubach K, Zabel P, Stüber F, (1998) Gender differences in human sepsis. Arch Surg (Chic, Ill: 1960133:: 1200-1205.
91. Merkel S, Alexander S, Zufall E, Oliver J, Huet-Hudson Y, (2001) Essential role for estrogen in protection against Vibrio vulnificus-induced endotoxic shock. Infect Immun 69: 6119-6122. doi:10.1128/IAI.69.10.6119-6122.2001. PubMed: 11553550.
92. Moxley G, Posthuma D, Carlson P, Estrada E, Han J, et al. (2002) Sexual dimorphism in innate immunity. Arthritis Rheum 46: 250-258. doi:10.1002/1529-0131(200201)46:1. PubMed: 11817599.
93. Marriott I, Bost K, Huet-Hudson Y, (2006) Sexual dimorphism in expression of receptors for bacterial lipopolysaccharides in murine macrophages: a possible mechanism for gender-based differences in endotoxic shock susceptibility. J Reprod Immunol 71: 12-27. doi:10.1016/j.jri.2006.01.004. PubMed: 16574244.
94. Kahlke V, Angele M, Ayala A, Schwacha M, Cioffi W, et al. (2000) Immune dysfunction following trauma-haemorrhage: influence of gender and age. Cytokine 12: 69-77. doi:10.1006/cyto.1999.0511. PubMed: 10623445.
95. Saia R, Anselmo-Franci J, Carnio E, (2008) Hypothermia during endotoxemic shock in female mice lacking inducible nitric oxide synthase. Shock (Augusta, Ga) 29: 119-126.
96. Walker Q, Cabassa J, Kaplan K, Li S, Haroon J, et al. (2001) Sex differences in cocaine-stimulated motor behavior: disparate effects of gonadectomy. Neuropsychopharmacol Off Publ American College Of Neuropsychopharmacology 25: 118-130. doi:10.1016/S0893-133X(00)00248-7.
97. Walker Q, Francis R, Cabassa J, Kuhn C, (2001) Effect of ovarian hormones and estrous cycle on stimulation of the hypothalamo-pituitary-adrenal axis by cocaine. J Pharmacol Exp Ther 297: 291-298. PubMed: 11259556.
98. Seok J, Warren H, Cuenca A, Mindrinos M, Baker H, et al. (2013) Genomic responses in mouse models poorly mimic human inflammatory diseases. Proc Natl Acad Sci U S A 110: 3507-3512. doi:10.1073/pnas.1222878110. PubMed: 23401516.
99. Copeland S, Warren HS, Lowry SF, Calvano SE, Remick D, (2005) Acute inflammatory response to endotoxin in mice and humans. Clin Diagn Lab Immunol 12: 60-67. PubMed: 15642986.
100. Weaver JD, Huang MH, Albert M, Harris T, Rowe JW, et al. (2002) Interleukin-6 and risk of cognitive decline: MacArthur studies of successful aging. Neurology 59: 371-378. doi:10.1212/WNL.59.3.371. PubMed: 12177370.
101. Wright CB, Sacco RL, Rundek TR, Delman JB, Rabbani LE, et al. (2006) Interleukin-6 is associated with cognitive function: the Northern Manhattan Study. J Stroke Cerebrovasc Dis 15: 34-38. doi:10.1016/j.jstrokecerebrovasdis.2005.08.009. PubMed: 16501663.
102. Engelhart MJ, Geerlings MI, Meijer J, Kiliaan A, Ruitenberg A, et al. (2004) Inflammatory proteins in plasma and the risk of dementia: the rotterdam study. Arch Neurol 61: 668-672. doi:10.1001/archneur.61.5.668. PubMed: 15148142.
103. Dinarello CA, (2009) Immunological and inflammatory functions of the interleukin-1 family. Annu Rev Immunol 27: 519-550. doi:10.1146/annurev.immunol.021908.132612. PubMed: 19302047.
104. Yirmiya R, Goshen I, (2011) Immune modulation of learning, memory, neural plasticity and neurogenesis. Brain Behav Immun 25: 181-213. doi:10.1016/j.bbi.2011.07.012. PubMed: 20970492.
105. Cunningham C, Sanderson DJ, (2008) Malaise in the water maze: untangling the effects of LPS and IL-1beta on learning and memory. Brain Behav Immun 22: 1117-1127. doi:10.1016/j.bbi.2008.05.007. PubMed: 18640811.
106. Pickering M, O'Connor JJ, (2007) Pro-inflammatory cytokines and their effects in the dentate gyrus. Prog Brain Res 163: 339-354. doi:10.1016/S0079-6123(07)63020-9. PubMed: 17765728.
107. Cunningham AJ, Murray CA, O'Neill LAJ, Lynch MA, O'Connor JJ, (1996) Interleukin-1β (IL-1β) and tumour necrosis factor (TNF) inhibit long-term potentiation in the rat dentate gyrus in vitro. Neurosci Lett 203: 17-20. doi:10.1016/0304-3940(95)12252-4. PubMed: 8742036.
108. Barrientos RM, Higgins EA, Sprunger DB, Watkins LR, Rudy JW, et al. (2002) Memory for context is impaired by a post context exposure injection of interleukin-1beta into dorsal hippocampus. Behav Brain Res 134: 291-298. doi:10.1016/S0166-4328(02)00043-8. PubMed: 12191816.
109. Hein AM, Stasko MR, Matousek SB, Scott-McKean JJ, Maier SF, et al. (2010) Sustained hippocampal IL-1beta overexpression impairs contextual and spatial memory in transgenic mice. Brain Behav Immun 24: 243-253. doi:10.1016/j.bbi.2009.10.002. PubMed: 19825412.
110. Fiore M, Probert L, Kollias G, Akassoglou K, Alleva E, et al. (1996) Neurobehavioral alterations in developing transgenic mice expressing TNF-alpha in the brain. Brain Behav Immun 10: 126-138. doi:10.1006/brbi.1996.0013. PubMed: 8811936.
111. Cibelli M, Fidalgo AR, Terrando N, Ma D, Monaco C, et al. (2010) Role of interleukin-1beta in postoperative cognitive dysfunction. Ann Neurol 68: 360-368. doi:10.1002/ana.22082. PubMed: 20818791.
112. Terrando N, Monaco C, Ma D, Foxwell BM, Feldmann M, et al. (2010) Tumor necrosis factor-alpha triggers a cytokine cascade yielding postoperative cognitive decline. Proc Natl Acad Sci U S A 107: 20518-20522. doi:10.1073/pnas.1014557107. PubMed: 21041647.
113. Sparkman NL, Buchanan JB, Heyen JR, Chen J, Beverly JL, et al. (2006) Interleukin-6 facilitates lipopolysaccharide-induced disruption in working memory and expression of other proinflammatory cytokines in hippocampal neuronal cell layers. J Neurosci 26: 10709-10716. doi:10.1523/JNEUROSCI.3376-06.2006. PubMed: 17050710.
114. Cunningham C, Wilcockson DC, Campion S, Lunnon K, Perry VH, (2005) Central and systemic endotoxin challenges exacerbate the local inflammatory response and increase neuronal death during chronic neurodegeneration. J Neurosci 25: 9275-9284. doi:10.1523/JNEUROSCI.2614-05.2005. PubMed: 16207887.
115. Godbout JP, Chen J, Abraham J, Richwine AF, Berg BM, et al. (2005) Exaggerated neuroinflammation and sickness behavior in aged mice following activation of the peripheral innate immune system. FASEB J 19: 1329-1331. PubMed: 15919760.
116. Chen J, Buchanan JB, Sparkman NL, Godbout JP, Freund GG, et al. (2008) Neuroinflammation and disruption in working memory in aged mice after acute stimulation of the peripheral innate immune system. Brain Behav Immun 22: 301-311. doi:10.1016/j.bbi.2007.08.014. PubMed: 17951027.
117. Barrientos RM, Higgins EA, Biedenkapp JC, Sprunger DB, Wright-Hardesty KJ, et al. (2006) Peripheral infection and aging interact to impair hippocampal memory consolidation. Neurobiology of Aging 27: 723-732. doi:10.1016/j.neurobiolaging.2005.03.010. PubMed: 15893410.
118. Chapman TR, Barrientos RM, Ahrendsen JT, Maier SF, Patterson SL, (2010) Synaptic Correlates of Increased Cognitive Vulnerability with Aging: Peripheral Immune Challenge and Aging Interact to Disrupt Theta-Burst Late-Phase Long-Term Potentiation in Hippocampal Area CA1. J Neurosci 30: 7598-7603. doi:10.1523/JNEUROSCI.5172-09.2010. PubMed: 20519534.
119. Holmes C, Cunningham C, Zotova E, Culliford D, Perry VH, (2011) Proinflammatory cytokines, sickness behavior, and Alzheimer disease. Neurology 77: 212-218. doi:10.1212/WNL.0b013e318225ae07. PubMed: 21753171.
120. George J, Bleasdale S, Singleton SJ, (1997) Causes and prognosis of delirium in elderly patients admitted to a district general hospital. Age Ageing 26: 423-427.
121. Swiergiel AH, Dunn AJ, (2007) Effects of interleukin-1beta and lipopolysaccharide on behavior of mice in the elevated plus-maze and open field tests. Pharmacol Biochem Behav 86: 651-659. doi:10.1016/j.pbb.2007.02.010. PubMed: 17360031.
122. Elander L, Engstrom L, Hallbeck M, Blomqvist A, (2007) IL-1beta and LPS induce anorexia by distinct mechanisms differentially dependent on microsomal prostaglandin E synthase-1. Am J Physiol Regul Integr Comp Physiol 292: R258-R267. PubMed: 16946079.
123. Mormède C, Castanon N, Médina C, Dantzer R, (2003) Conditioned place aversion with interleukin-1[beta] in mice is not associated with activation of the cytokine network. Brain Behav Immun 17: 110-120. doi:10.1016/S0889-1591(02)00054-5. PubMed: 12676573.
124. Bluthé RM, Pawlowski M, Suarez S, Parnet P, Pittman Q, et al. (1994) Synergy between tumor necrosis factor α and interleukin-1 in the induction of sickness behavior in mice. Psychoneuroendocrinology 19: 197-207. doi:10.1016/0306-4530(94)90009-4. PubMed: 8190839.