The inflammation hypothesis in geriatric depression

International Journal of Geriatric Psychiatry

Volumn 26, Issue 11, 2011, Pages 1109-1118

  Alexopoulos, George S ^a   Morimoto, Sarah Shizuko ^a  

^a The Cornell Institute of Geriatric Psychiatry   (United States)

Author keywords

aging; depression; geriatrics; immunity

Indexed keywords

ANTIDEPRESSANT AGENT; ANTIINFLAMMATORY AGENT; BIOLOGICAL MARKER; CELECOXIB; DESIPRAMINE; ETANERCEPT; FLUOXETINE; MIANSERIN; MINOCYCLINE; MOCLOBEMIDE; PAROXETINE; REBOXETINE; SERTRALINE; TRAZODONE; VENLAFAXINE;

AGING; ANTIINFLAMMATORY ACTIVITY; CENTRAL NERVOUS SYSTEM; COGNITION; COMORBIDITY; DEPRESSION; DRUG EFFICACY; EMOTION; GERIATRIC DEPRESSION; GERIATRIC DISORDER; HUMAN; IMMUNE RESPONSE; NERVOUS SYSTEM INFLAMMATION; PERIPHERAL NERVOUS SYSTEM; REVIEW; VASCULAR DEPRESSION;

AGED; AGING; ANTI-INFLAMMATORY AGENTS; ANTIDEPRESSIVE AGENTS; BRAIN; CENTRAL NERVOUS SYSTEM; DEPRESSIVE DISORDER; ENCEPHALITIS; HUMANS; INFLAMMATION MEDIATORS;

EID: 80055009010     PISSN: 08856230     EISSN: 10991166     Source Type: Journal    
DOI: 10.1002/gps.2672     Document Type: Review

References (119)

1. Akhondzadeh S, Jafari S, Raisi F, et al,. 2009. Clinical trial of adjunctive celecoxib treatment in patients with major depression: a double blind and placebo controlled trial. Depress Anxiety 26: 607-611.
2. Alexopoulos GS,. 2002. Frontostriatal and limbic dysfunction in late-life depression. Am J Geriatr Psychiatry 10 (6): 687-695.
3. Alexopoulos GS,. 2005. Depression in the elderly. Lancet 365 (9475): 1961-1970.
4. Alexopoulos GS, Kelly R.E. Jr,. 2009. Research advances in geriatric depression. World Psychiatry 8 (3): 140-149.
5. Apostolakis S, Vogiatzi K, Krambovitis E, Spandidos DA, 2008. IL-1 cytokines in cardiovascular disease: diagnostic, prognostic and therapeutic implications. Cardiovasc Hematol Agents Med Chem 6: 150-158.
6. Banati RB, Graeber MB,. 1994. Surveillance, intervention and cytotoxicity: is there a protective role of microglia? Dev Neurosci 16 (3-4): 114-127.
7. Banks WA,. 2001. Cytokine's CVs and the Blood-Brain Barrier. Academic Press: San Diego.
8. Basterzi AD, Aydemir C, Kisa C, et al,. 2005. IL-6 levels decrease with SSRI treatment in patients with major depression. Hum Psychopharmacol 20: 473-476.
9. Baune BT, Dannlowski U, Domschke K, et al,. The interleukin 1 beta (IL1B) gene is associated with failure to achieve remission and impaired emotion processing in major depression. Biol Psychiatry 67: 543-549.
10. Blalock JE,. 1994. The syntax of immune-neuroendocrine communication. Immunol Today 15 (11): 504-511.
11. Blasko I, Stampfer-Kountchev M, Robatscher P, et al,. 2004. How chronic inflammation can affect the brain and support the development of Alzheimer's disease in old age: the role of microglia and astrocytes. Aging Cell 3: 169-176.
12. Brambilla F, Maggioni M,. 1998. Blood levels of cytokines in elderly patients with major depressive disorder. Acta Psychiatr Scand 97 (4): 309-313.
13. Bremmer MA, Beekman AT, Deeg DJ, et al,. 2008. Inflammatory markers in late-life depression: results from a population-based study. J Affect Disord 106: 249-255.
14. Buchanan JB, Sparkman NL, Chen J, Johnson RW,. 2008. Cognitive and neuroinflammatory consequences of mild repeated stress are exacerbated in aged mice. Psychoneuroendocrinology 33: 755-765.
15. Cacci E, Claasen JH, Kokaia Z,. 2005. Microglia-derived tumor necrosis factor-alpha exaggerates death of newborn hippocampal progenitor cells in vitro. J Neurosci Res 80: 789-797.
16. Calabrese JR, Skwerer RG, Barna B, et al,. 1986. Depression, immunocompetence, and prostaglandins of the E series. Psychiatry Res 17: 41-47.
17. Capuron L, Pagnoni G, Demetrashvili M, et al,. 2005. Anterior cingulate activation and error processing during interferon-alpha treatment. Biol Psychiatry 58: 190-196.
18. Carpentier PA, Palmer TD,. 2009. Immune influence on adult neural stem cell regulation and function. Neuron 64 (1): 79-92.
19. Cesari M, Penninx BW, Newman AB, et al,. 2003. Inflammatory markers and onset of cardiovascular events: results from the Health ABC study. Circulation 108: 2317-2322.
20. Chen M, Ona VO, Li M, et al,. 2000. Minocycline inhibits caspase-1 and caspase-3 expression and delays mortality in a transgenic mouse model of Huntington disease. Nat Med 6: 797-801.
21. Collantes-Estevez E, Munoz-Villanueva MC, Canete-Crespillo JD, et al,. 2003. Infliximab in refractory spondyloarthropathies: a multicentre 38 week open study. Ann Rheum Dis 62: 1239-1240.
22. Conde JR, Streit WJ,. 2006. Effect of aging on the microglial response to peripheral nerve injury. Neurobiol Aging 27 (10): 1451-1461.
23. Darlington CL,. 2005. Astrocytes as targets for neuroprotective drugs. Curr Opin Investig Drugs 6 (7): 700-703.
24. Dentino AN, Pieper CF, Rao MK, et al,. 1999. Association of interleukin-6 and other biologic variables with depression in older people living in the community. J Am Geriatr Soc 47: 6-11.
25. Dilger RN, Johnson RW,. 2008. Aging, microglial cell priming, and the discordant central inflammatory response to signals from the peripheral immune system. J Leukoc Biol 84 (4): 932-939.
26. Diniz BS, Teixeira AL, Talib L, Gattaz WF,. Interleukin-1beta serum levels is increased in antidepressant-free elderly depressed patients. Am J Geriatr Psychiatry 18: 172-176.
27. Diniz BS, Teixeira AL, Talib LL, et al,., Increased soluble TNF receptor 2 in antidepressant-free patients with late-life depression. J Psychiatr Res 44: 917-920. Epub: 2010/03/27.
28. Dowlati Y, Herrmann N, Swardfager W, et al,. A meta-analysis of cytokines in major depression. Biol Psychiatry 67: 446-457.
29. Eller T, Vasar V, Shlik J, et al,. 2008. Pro-inflammatory cytokines and treatment response to escitalopram in major depressive disorder. Prog Neuropsychopharmacol Biol Psychiatry 32: 445-450.
30. Ershler WB,. 1993. Interleukin-6: a cytokine for gerontologists. J Am Geriatr Soc 41 (2): 176-181.
31. Ershler WB, Sun WH, Binkley N, et al,. 1993. Interleukin-6 and aging: blood levels and mononuclear cell production increase with advancing age and in vitro production is modifiable by dietary restriction. Lymphokine Cytokine Res 12: 225-230.
32. Ferrucci L, Harris TB, Guralnik M, et al,. 1999. Serum IL-6 level and the development of disability in older persons. J Am Geriatr Soc 47: 639-646.
33. Flugel A, Bradl M, Kreutzberg GW, Graeber MB,. 2001. Transformation of donor-derived bone marrow precursors into host microglia during autoimmune CNS inflammation and during the retrograde response to axotomy. J Neurosci Res 66: 74-82.
34. Frank MG, Baratta MV, Sprunger DB, Watkins LR, Maier SF,. 2007. Microglia serve as a neuroimmune substrate for stress-induced potentiation of CNS pro-inflammatory cytokine responses. Brain Behav Immun 21: 47-59.
35. Frommberger UH, Bauer J, Haselbauer P, et al,. 1997. Interleukin-6-(IL-6) plasma levels in depression and schizophrenia: comparison between the acute state and after remission. Eur Arch Psychiatry Clin Neurosci 247: 228-233.
36. Gehrmann J, Banati RB, Kreutzberg GW, et al,. 1993. Microglia in the immune surveillance of the brain: human microglia constitutively express HLA-DR molecules. J Neuroimmunol 48: 189-198.
37. Gimeno D, Kivimaki M, Brunner EJ, et al,. 2009. Associations of C-reactive protein and interleukin-6 with cognitive symptoms of depression: 12-year follow-up of the Whitehall II study. Psychol Med 39: 413-423.
38. Giulian D, Baker TJ, Shih LC, et al,. 1986. Interleukin 1 of the central nervous system is produced by ameboid microglia. J Exp Med 164 (2): 594-604.
39. Godbout JP, Chen J, Abraham J, et al,. 2005. Exaggerated neuroinflammation and sickness behavior in aged mice following activation of the peripheral innate immune system. FASEB J 19: 1329-1331.
40. Godbout JP, Johnson RW,. 2006. Age and neuroinflammation: a lifetime of psychoneuroimmune consequences. Neurol Clin 24 (3): 521-538.
41. Goehler LE, Gaykema RP, Hansen MK, et al,. 2000. Vagal immune-to-brain communication: a visceral chemosensory pathway. Auton Neurosci 85: 49-59.
42. Graeber MB, Tetzlaff W, Streit WJ, Kreutzberg GW, 1988. Microglial cells but not astrocytes undergo mitosis following rat facial nerve axotomy. Neurosci Lett 85: 317-321.
43. Grassi-Oliveira R, Brietzke E, Pezzi JC, et al,. 2009. Increased soluble tumor necrosis factor-alpha receptors in patients with major depressive disorder. Psychiatry Clin Neurosci 63: 202-208.
44. Gruver AL, Hudson LL, Sempowski GD, et al,. 2007. Immunosenescence of ageing. J Pathol 211: 144-156.
45. Hager K, Machein U, Krieger S, et al,. 1994. Interleukin-6 and selected plasma proteins in healthy persons of different ages. Neurobiol Aging 15 (6): 771-772.
46. Harris TB, Ferrucci L, Tracy RP, et al,. 1999. Associations of elevated interleukin-6 and C-reactive protein levels with mortality in the elderly. Am J Med 106: 506-512.
47. Harrison NA, Brydon L, Walker C, et al,. 2009. Inflammation causes mood changes through alterations in subgenual cingulate activity and mesolimbic connectivity. Biol Psychiatry 66 (5): 407-414.
48. Heyes MP, Saito K, Markey SP,. 1992. Human macrophages convert L-tryptophan into the neurotoxin quinolinic acid. Biochem J 283 (Pt 3): 633-635.
49. Hodgkin PD, Bond MW, O'Garra A, et al,. 1988. Identification of IL-6 as a T cell-derived factor that enhances the proliferative response of thymocytes to IL-4 and phorbol myristate acetate. J Immunol 141 (1): 151-157.
50. Howren MB, Lamkin DM, Suls J,. 2009. Associations of depression with C-reactive protein, IL-1, and IL-6: a meta-analysis. Psychosom Med 71 (2): 171-186.
51. Iosif RE, Ekdahl CT, Ahlenius H, et al,. 2006. Tumor necrosis factor receptor 1 is a negative regulator of progenitor proliferation in adult hippocampal neurogenesis. J Neurosci 26: 9703-9712.
52. Johnson JD, O'Connor KA, Deak T, et al,. 2002. Prior stressor exposure sensitizes LPS-induced cytokine production. Brain Behav Immun 16: 461-476.
53. Jones TB, Lucin KM, Popovich PG,. 2008. The Immune System of the Brain. In The Hypothalamus-Pituitary-Adrenal Axis., Del Rey A, Chrousos G, Besedovsky H, (eds). Elsevier.
54. Kagaya A, Kugaya A, Takebayashi M, et al,. 2001. Plasma concentrations of interleukin-1beta, interleukin-6, soluble interleukin-2 receptor and tumor necrosis factor alpha of depressed patients in Japan. Neuropsychobiology 43: 59-62.
55. Kim YK, Na KS, Shin KH, et al,. 2007. Cytokine imbalance in the pathophysiology of major depressive disorder. Prog Neuropsychopharmacol Biol Psychiatry 31: 1044-1053.
56. Kreutzberg GW,. 1996. Microglia: a sensor for pathological events in the CNS. Trends Neurosci 19: 312-318.
57. Kritchevsky SB, Cesari M, Pahor M,. 2005. Inflammatory markers and cardiovascular health in older adults. Cardiovasc Res 66: 265-275.
58. Kubera M, Holan V, Basta-Kaim A, et al,. 1998. Effect of desipramine on immunological parameters in mice, and their reversal by stress. Int J Immunopharmacol 20: 429-438.
59. Kubera M, Kenis G, Bosmans E, et al,. 2000. Effects of serotonin and serotonergic agonists and antagonists on the production of interferon-gamma and interleukin-10. Neuropsychopharmacology 23: 89-98.
60. Kubera M, Kenis G, Bosmans E, et al,. 2000. Plasma levels of interleukin-6, interleukin-10, and interleukin-1 receptor antagonist in depression: comparison between the acute state and after remission. Pol J Pharmacol 52: 237-241.
61. Kubera M, Kenis G, Budziszewska B, et al,. 2001. Lack of a modulatory effect of imipramine on glucocorticoid-induced suppression of interferon-gamma and interleukin-10 production in vitro. Pol J Pharmacol 53: 289-294.
62. Lee CK, Weindruch R, Prolla TA,. 2000. Gene-expression profile of the ageing brain in mice. Nat Genet 25: 294-297.
63. Lee KM, Kim YK,. 2006. The role of IL-12 and TGF-beta1 in the pathophysiology of major depressive disorder. Int Immunopharmacol 6: 1298-1304.
64. Levkovitz Y, Mendlovich S, Riwkes S, et al,. A double-blind, randomized study of minocycline for the treatment of negative and cognitive symptoms in early-phase schizophrenia. J Clin Psychiatry 71: 138-149.
65. Lin A, Song C, Kenis G, et al,. 2000. The in vitro immunosuppressive effects of moclobemide in healthy volunteers. J Affect Disord 58: 69-74.
66. Lindemann RA,. 1991. The regulatory effects of monocytes on human natural killer cells activated by lipopolysaccharides. J Periodontal Res 26: 486-490.
67. Lindqvist D, Janelidze S, Hagell P, et al,. 2009. Interleukin-6 is elevated in the cerebrospinal fluid of suicide attempters and related to symptom severity. Biol Psychiatry 66: 287-292.
68. Linnoila MW, Whorton R, Rubinow DR, et al,. 1983. CSF prostoglandin levels in depressed and schizophrenic patients. Arch Gen Psychiatry 40: 405-406.
69. Lu T, Pan Y, Kao SY, et al,. 2004. Gene regulation and DNA damage in the ageing human brain. Nature 429 (6994): 883-891.
70. Lucin KM, Wyss-Coray T,. 2009. Immune activation in brain aging and neurodegeneration: too much or too little? Neuron 64 (1): 110-122.
71. Lutgendorf SK, Garand L, Buckwalter KC, et al,. 1999. Life stress, mood disturbance, and elevated interleukin-6 in healthy older women. J Gerontol A Biol Sci Med Sci 54: M434-M439.
72. Maes M,. Depression is an inflammatory disease, but cell-mediated immune activation is the key component of depression. Prog Neuropsychopharmacol Biol Psychiatry Epub: 2010/07/06.
73. Maes M,. 1993. A review on the acute phase response in major depression. Rev Neurosci 4: 407-416.
74. Maes M, Bosmans E, De Jongh R, et al,. 1997. Increased serum IL-6 and IL-1 receptor antagonist concentrations in major depression and treatment resistant depression. Cytokine 9: 853-858.
75. Maes M, Bosmans E, Scharpe S, et al,. 1995. Plasma soluble interleukin-2-receptor in depression: relationships to plasma neopterin and serum IL-2 concentrations and HPA-axis activity. Eur Psychiatry 10: 397-403.
76. Maes M, Bosmans E, Suy E, et al,. 1990. Immune disturbances during major depression: upregulated expression of interleukin-2 receptors. Neuropsychobiology 24: 115-120.
77. Maes M, Meltzer HY, Scharpe S, et al,. 1993. Relationships between lower plasma L-tryptophan levels and immune-inflammatory variables in depression. Psychiatry Res 49: 151-165.
78. Maes M, Song C, et al,. 1999. Negative immunoregulatory effects of antidepressants: inhibition of interferon-gamma and stimulation of interleukin-10 secretion. Neuropsychopharmacology 20 (4): 370-379.
79. Maggio M, Guralnik JM, Lin AH, et al,. 2006. Interleukin-6 in aging and chronic disease: a magnificent pathway. J Gerontol A Biol Sci Med Sci 61: 575-584.
80. Maier SF, Goehler LE, Fleshner M, Watkins LR,. 1998. The role of the vagus nerve in cytokine-to-brain communication. Ann N Y Acad Sci 840: 289-300.
81. Maier SF, Watkins LR,. 2003. Immune-to-central nervous system communication and its role in modulating pain and cognition: Implications for cancer and cancer treatment. Brain Behav Immun 17 (Suppl 1): S125-S1231.
82. 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.
83. Mayer P, Geissler K, Valent P, et al,. 1991. Recombinant human interleukin 6 is a potent inducer of the acute phase response and elevates the blood platelets in nonhuman primates. Exp Hematol 19: 688-696.
84. Mellor AL, Munn DH,. 1999. Tryptophan catabolism and T-cell tolerance: immunosuppression by starvation? Immunol Today 20 (10): 469-473.
85. Mikova O, Yakimova R, Bosmans E, et al,. 2001. Increased serum tumor necrosis factor alpha concentrations in major depression and multiple sclerosis. Eur Neuropsychopharmacol 11 (3): 203-208.
86. Milaneschi Y, Corsi AM, Penninx BW, et al,. 2009. Interleukin-1 receptor antagonist and incident depressive symptoms over 6 years in older persons: the InCHIANTI study. Biol Psychiatry 65: 973-978.
87. Miyaoka T, Yasukawa R, Yasuda H, et al,. 2008. Minocycline as adjunctive therapy for schizophrenia: an open-label study. Clin Neuropharmacol 31: 287-292.
88. Molina-Hernandez M, Tellez-Alcantara NP, Perez-Garcia J, et al,. 2008. Antidepressant-like actions of minocycline combined with several glutamate antagonists. Prog Neuropsychopharmacol Biol Psychiatry 32: 380-386.
89. Monje ML, Toda H, Palmer TD,. 2003. Inflammatory blockade restores adult hippocampal neurogenesis. Science 302: 1760-1765.
90. Muller N, Schwarz MJ, Dehning S, et al,. 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.
91. Nishino S, Ueno R, Ohishi K, Sakai T, Hayaishi O,. 1998. Neurotrophins regulate the function of cultured microglia. Glia 24: 272-289.
92. Nishino S, Ueno R, Ohishi K, Sakai T, Hayaishi O,. 1989. Salivary prostaglandin concentrations: possible state indicators for major depression. Am J Psychiatry 146: 365-368.
93. O'Brien SM, Scully P, Fitzgerald P, Scott LV, Dinan TG,. 2007. Plasma cytokine profiles in depressed patients who fail to respond to selective serotonin reuptake inhibitor therapy. J Psychiatr Res 41: 326-331.
94. Pae CU, Marks DM, Han C, Patkar AA,. 2008. Does minocycline have antidepressant effect? Biomed Pharmacother 62: 308-311.
95. Penninx BW, Kritchevsky SB, Yaffe K, et al,. 2003. Inflammatory markers and depressed mood in older persons: results from the Health, Aging and Body Composition study. Biol Psychiatry 54: 566-572.
96. Plane JM, Shen Y, Pleasure DE, Deng W,. 2010. Prospects for Minocycline Neuroprotection. Arch Neurol. 67: 1442-1448.
97. Romeo HE, Tio DL, Rahman SU, Chiappelli F, Taylor AN,. 2001. The glossopharyngeal nerve as a novel pathway in immune-to-brain communication: relevance to neuroimmune surveillance of the oral cavity. J Neuroimmunol 115: 91-100.
98. Roubenoff R, Parise H, Payette HA, et al,. 2003. Cytokines, insulin-like growth factor 1, sarcopenia, and mortality in very old community-dwelling men and women: the Framingham Heart Study. Am J Med 115: 429-435.
99. Roumestan C, Michel A, Bichon F, et al,. 2007. Anti-inflammatory properties of desipramine and fluoxetine. Respir Res 8: 35.
100. Schwarcz R, Whetsell WO Jr, Mangano RM,. 1983. Quinolinic acid: an endogenous metabolite that produces axon-sparing lesions in rat brain. Science 219: 316-338.
101. 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.
102. Sluzewska A, Rybakowski J, Bosmans E, et al,. 1996. Indicators of immune activation in major depression. Psychiatry Res 64: 161-167.
103. Song C, Lin A, Bonaccorso S, et al,. 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.
104. Sparkman NL, Johnson RW,. 2008. Neuroinflammation associated with aging sensitizes the brain to the effects of infection or stress. Neuroimmunomodulation 15 (4-6): 323-330.
105. Stone TW, Behan WM,. 2007. Interleukin-1beta but not tumor necrosis factor-alpha potentiates neuronal damage by quinolinic acid: protection by an adenosine A2A receptor antagonist. J Neurosci Res 85 (5): 1077-1085.
106. Streit WJ, Miller KR, Lopes KO, Njie E,. 2008. Microglial degeneration in the aging brain-bad news for neurons? Front Biosci 13: 3423-3438.
107. Szuster-Ciesielska A, Tustanowska-Stachura A, et al,. 2003. In vitro immunoregulatory effects of antidepressants in healthy volunteers. Pol J Pharmacol 55 (3): 353-362.
108. Terao A, Apte-Deshpande A, Dousman L, et al,. 2002. Immune response gene expression increases in the aging murine hippocampus. J Neuroimmunol 132: 99-112.
109. Thomas AJ, Davis S, Morris C, et al,. 2005. Increase in interleukin-1beta in late-life depression. Am J Psychiatry 162: 175-177.
110. Tiemeier H, Hofman A, van Tuijl HR, et al,. 2003. Inflammatory proteins and depression in the elderly. Epidemiology 14: 103-107.
111. Tyring S, Gottlieb A, Papp K, et al,. 2006. Etanercept and clinical outcomes, fatigue, and depression in psoriasis: double-blind placebo-controlled randomised phase III trial. Lancet 367: 29-35.
112. Wang J, Asensio VC, Campbell IL,. 2002. Cytokines and chemokines as mediators fo protection and injury in the central nervous system assessed in transgenic mice. Curr Top Microbiol Immunol 265: 24-48.
113. Weaver JD, Huang MH, Albert M, et al,. 2002. Interleukin-6 and risk of cognitive decline: MacArthur studies of successful aging. Neurology 59: 371-378.
114. Wei J, Xu H, Davies JL, Hemmings GP,. 1992. Increase of plasma IL-6 concentration with age in healthy subjects. Life Sci 51: 1953-1956.
115. Xie Z, Morgan TE, Rozovsky I, Finch CE,. 2003. Aging and glial responses to lipopolysaccharide in vitro: greater induction of IL-1 and IL-6, but smaller induction of neurotoxicity. Exp Neurol 182: 135-141.
116. Yang I, Han SJ, Kaur G, Crane C, Parsa, AT,. 2010. The role of microglia in central nervous system immunity and glioma immunology. J Clin Neurosci 17: 6-10.
117. Ye SM, Johnson RW,. 1999. Increased interleukin-6 expression by microglia from brain of aged mice. J Neuroimmunol 93: 139-148.
118. Ye SM, Johnson RW,. 2001. An age-related decline in interleukin-10 may contribute to the increased expression of interleukin-6 in brain of aged mice. Neuroimmunomodulation 9: 183-192.
119. Yirmiya R, Tio DL, Taylor AN,. 1996. Effects of fetal alcohol exposure on fever, sickness behavior, and pituitary-adrenal activation induced by interleukin-1 beta in young adult rats. Brain Behav Immun 10: 205-220.