title: Central and peripheral cytokines mediate immune-brain connectivity.
abstract: The immune system is a homeostatic system that contributes to maintain the constancy of the molecular and cellular components of the organism. Immune cells can detect the intrusion of foreign antigens or alteration of self-components and send information to the central nervous system (CNS) about this kind of perturbations, acting as a receptor sensorial organ. The brain can respond to such signals by emitting neuro/endocrine signals capable of affecting immune reactivity. Thus, the immune system, as other physiologic systems, is under brain control. Under disease conditions, when priorities for survival change, the immune system can, within defined limits, reset brain-integrated neuro-endocrine mechanisms in order to favour immune processes at the expenses of other physiologic systems. In addition, some cytokines initially conceived as immune products, such as IL-1 and IL-6, are also produced in the "healthy" brain by glial cells and even by some neurons. These and other cytokines have the capacity to affect synaptic plasticity acting as mediators of interactions between astrocytes and pre- and post-synaptic neurons that constitute what is actually defined as a tripartite synapse. Since the production of cytokines in the brain is affected by peripheral immune and central neural signals, it is conceivable that tripartite synapses can, in turn, serve as a relay system in immune-CNS communication.
authors.affiliation: Department Immunophysiology, Institute of Physiology and Pathophysiology, Medical Faculty, Deutschhausstrasse 2, 35037 Marburg, Germany. besedovs@mailer.uni-marburg.de
authors.forename: Hugo O
authors.initials: HO
authors.lastname: Besedovsky
authors.forename: Adriana
authors.initials: A
authors.lastname: del Rey
mesh_terms: D000818:Animals; D001921:Brain / Q000033:anatomy & histology / Q000276:immunology* / Q000502:physiology; D016207:Cytokines / Q000276:immunology*; D005947:Glucose / Q000378:metabolism; D051272:Glucose Transporter Type 1 / Q000378:metabolism; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D006801:Humans; D007031:Hypothalamus / Q000166:cytology / Q000276:immunology; D007107:Immune System / Q000276:immunology* / Q000502:physiology; D007375:Interleukin-1 / Q000276:immunology; D015850:Interleukin-6 / Q000276:immunology; D015398:Signal Transduction / Q000502:physiology
chemical_list: D016207:Cytokines; D051272:Glucose Transporter Type 1; D051275:Glucose Transporter Type 4; D007375:Interleukin-1; D015850:Interleukin-6; D005947:Glucose
references.citation: J Immunol. 2001 Dec 15;167(12):6827-33
references.pmid: 11739499
references.citation: Endocrinology. 2002 May;143(5):1761-8
references.pmid: 11956158
references.citation: FASEB J. 2004 Nov;18(14):1788-90
references.pmid: 15345694
references.citation: Proc Natl Acad Sci U S A. 2006 Oct 24;103(43):16039-44
references.pmid: 17035503
references.citation: Glia. 2008 Jul;56(9):975-89
references.pmid: 18383346
references.citation: Endocrinology. 2004 Nov;145(11):5150-6
references.pmid: 15297440
references.citation: J Endocrinol Invest. 1991 May;14(5):401-4
references.pmid: 1875016
references.citation: J Neurosci. 2004 Jul 21;24(29):6482-8
references.pmid: 15269258
references.citation: Learn Mem. 2000 Nov-Dec;7(6):400-12
references.pmid: 11112799
references.citation: Brain Res. 1993 Nov 19;628(1-2):227-34
references.pmid: 8313151
references.citation: Proc Natl Acad Sci U S A. 1998 Jun 23;95(13):7778-83
references.pmid: 9636227
references.citation: Nature. 2009 Feb 5;457(7230):675-7
references.pmid: 19194443
references.citation: J Neurochem. 2006 Nov;99(4):1049-61
references.pmid: 16899068
references.citation: Curr Pharm Des. 2005;11(8):963-72
references.pmid: 15777247
references.citation: Nature. 2010 Jan 14;463(7278):169-70
references.pmid: 20075911
references.citation: Brain Res. 1990 Aug 13;525(1):149-51
references.pmid: 2173960
references.citation: Synapse. 2000 Feb;35(2):151-9
references.pmid: 10611641
references.citation: Neurosci Lett. 1992 Nov 9;146(2):176-8
references.pmid: 1337194
references.citation: J Neurosci. 2009 Mar 18;29(11):3395-403
references.pmid: 19295146
references.citation: Shock. 2000 May;13(5):379-85
references.pmid: 10807013
references.citation: Eur J Pharmacol. 1990 Jun 8;181(3):323-6
references.pmid: 2166677
references.citation: Glia. 2007 Sep;55(12):1251-62
references.pmid: 17659524
references.citation: Biochem Biophys Res Commun. 2009 Jun 5;383(3):326-30
references.pmid: 19358832
references.citation: Proc Natl Acad Sci U S A. 2009 Apr 28;106(17):7119-24
references.pmid: 19359475
references.citation: Behav Brain Res. 2004 Aug 31;153(2):423-9
references.pmid: 15265638
references.citation: Arthritis Rheum. 2008 Oct;58(10):3090-9
references.pmid: 18821705
references.citation: Hippocampus. 2003;13(7):826-34
references.pmid: 14620878
references.citation: Brain Res. 1991 Nov 15;564(2):245-8
references.pmid: 1725767
references.citation: J Immunol. 1997 May 15;158(10):4714-20
references.pmid: 9144484
references.citation: J Neuroimmunol. 2009 Mar 31;208(1-2):46-53
references.pmid: 19211154
references.citation: Annu Rev Nutr. 2005;25:9-35
references.pmid: 16011457
references.citation: Psychoneuroendocrinology. 2007 Sep-Nov;32(8-10):1106-15
references.pmid: 17976923
references.citation: Neurobiol Learn Mem. 2002 Sep;78(2):379-89
references.pmid: 12431424
references.citation: Neuroscience. 2001;108(1):83-90
references.pmid: 11738133
references.citation: Am J Physiol Endocrinol Metab. 2008 Aug;295(2):E242-53
references.pmid: 18577699
references.citation: Am J Clin Nutr. 2009 Sep;90(3):875S-880S
references.pmid: 19571222
references.citation: J Immunol. 2008 Jun 15;180(12):7948-57
references.pmid: 18523258
references.citation: Glia. 2002 Jul;39(1):10-8
references.pmid: 12112371
references.citation: Brain Res. 2000 Dec 1;885(1):14-24
references.pmid: 11121525
references.citation: Brain Res. 1997 Feb 14;748(1-2):30-8
references.pmid: 9067442
references.citation: Brain Behav Immun. 2007 Jan;21(1):34-44
references.pmid: 17157762
references.citation: Nat Rev Immunol. 2005 Nov;5(11):844-52
references.pmid: 16239903
references.citation: Prog Neuropsychopharmacol Biol Psychiatry. 1998 Jan;22(1):1-33
references.pmid: 9533165
references.citation: Trends Neurosci. 2009 Aug;32(8):421-31
references.pmid: 19615761
references.citation: Infect Immun. 1996 Jan;64(1):108-12
references.pmid: 8557327
references.citation: Proc Natl Acad Sci U S A. 1989 Aug;86(15):5943-7
references.pmid: 2668949
references.citation: J Immunol. 1998 May 1;160(9):4242-7
references.pmid: 9574525