Cytokines, neurophysiology, neuropsychology, and psychiatric symptoms

Dialogues in Clinical Neuroscience

Volumn 5, Issue 2, 2003, Pages 139-153

  Schwarz, Markus J ^a  

^a UNIVERSITY OF MUNICH   (Germany)

Author keywords

Cytokine; Immunogenetics; Major depression; Psychoneuroimmunology; Schizophrenia; Sickness behavior

Indexed keywords

CYTOKINE; CYTOKINE RECEPTOR; NEUROPEPTIDE; NEUROTRANSMITTER; PROTEIN;

BEHAVIOR; BLOOD BRAIN BARRIER; BRAIN FUNCTION; HUMAN; HYPOTHALAMUS HYPOPHYSIS ADRENAL SYSTEM; ILLNESS BEHAVIOR; IMMUNE SYSTEM; IMMUNOGENETICS; MAJOR DEPRESSION; MENTAL DISEASE; NEUROPHYSIOLOGY; NEUROPSYCHOLOGY; NONHUMAN; PATHOPHYSIOLOGY; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN LOCALIZATION; PROTEIN STRUCTURE; PROTEIN TRANSPORT; REGULATORY MECHANISM; REVIEW; SCHIZOPHRENIA; SIGNAL TRANSDUCTION;

EID: 0042170353     PISSN: 12948322     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (194)

1. Metal'nikov S, Chorine V. Rôle des réflexes conditionnels dans l'immunité. Ann Inst Pasteur. 1926;40:893-900.
2. Ader R, Cohen N. Behaviorally conditioned immunosuppression. Psychosom Med. 1975;37:333-340.
3. Rasmussen AF, Marsh JT, Brill NQ. Increased susceptibility to herpes simplex in mice subjected to avoidance-learning stress or restraint. Proc Soc Exp Biol Med. 1957;96:183-189.
4. Besedovsky H, Sorkin E. Network of immune-neuroendocrine interactions. Clin Exp Immunol. 1977;27:1-12.
5. Williams JM, Peterson RG, Shea PA, Schmedtje JF, Bauer DC, Felten DL. Sympathetic innervation of murine thymus and spleen: evidence for a functional link between the nervous and immune systems. Brain Res Bull. 1981;6:83-94.
6. Felten DL, Felten SY, Bellinger DL, et al. Noradrenergic sympathetic neural interactions with the immune system: structure and function. Immunol Rev. 1987;100:225-260.
7. Berkenbosch F, van Oers J, del Rey A, Tilders F, Besedovsky H. Corticotropin-releasing factor-producing neurons in the rat activated by interleukin-1. Science. 1987;238:524-526.
8. Besedovsky H, del Rey A. Neuroendocrine and metabolic responses induced by interleukin-1. J Neurosci Res. 1987;18:172-178.
9. Sapolsky R, Rivier C, Yamamoto G, Plotsky P, Vale W. Interleukin-1 stimulates the secretion of hypothalamic corticotropin-releasing factor. Science. 1987;238:522-524.
10. Duff GW, Durum SK. The pyrogenic and mitogenic actions of interleukin-1 are related. Nature. 1983;304:449-451.
11. Krueger JM, Walter J, Dinarello CA, Wolff SM, Chedid L. Sleep-promoting effects of endogenous pyrogen (interleukin-1). Am J Physiol. 1984;246(6, pt 2):R994-R999.
12. McCarthy DO, Kluger MJ, Vander AJ. Effect of centrally administered interleukin-1 and endotoxin on food intake of fasted rats. Physiol Behav. 1986;36:745-749.
13. Chance WT, Fischer JE. Aphagic and adipsic effects of interleukin-1. Brain Res. 1991;568:261-264.
14. Crestani F, Seguy F, Dantzer R. Behavioural effects of peripherally injected interleukin-1: role of prostaglandins. Brain Res. 1991;542:330-335.
15. Smedley H, Katrak M, Sikora K, Wheeler T. Neurological effects of recombinant human interferon. BMJ (Clin Res Ed). 1983;286:262-264.
16. Spriggs DR, Sherman ML, Frei E III, Kufe DW. Clinical studies with tumour necrosis factor. Ciba Found Symp. 1987;131:206-227.
17. Kapas L, Krueger JM. Tumor necrosis factor-beta induces sleep, fever, and anorexia. Am J Physiol. 1992;263(3, pt 2):R703-R707.
18. Kapas L, Hong L, Cady AB, et al. Somnogenic, pyrogenic, and anorectic activities of tumor necrosis factor-alpha and TNF-alpha fragments. Am J Physiol. 1992;263(3, pt 2):R708-R715.
19. Dinarello CA, Bernheim HA, Duff GW, et al. Mechanisms of fever induced by recombinant human interferon. J Clin Invest. 1984;74:906-913.
20. Kimura M, Majde JA, Toth LA, Opp MR, Krueger JM. Somnogenic effects of rabbit and recombinant human interferons in rabbits. Am J Physiol. 1994;267(1, pt 2):R53-R61.
21. Ribeiro RC, Rill D, Roberson PK, et al. Continuous infusion of interleukin-2 in children with refractory malignancies. Cancer. 1993;72:623-628.
22. LeMay LG, Vander AJ, Kluger MJ. Role of interleukin 6 in fever in rats. Am J Physiol. 1990;258(3, pt 2):R798-R803.
23. Atkins MB, Robertson MJ, Gordon M, et al. Phase I evaluation of intravenous recombinant human interleukin 12 in patients with advanced malignancies. Clin Cancer Res. 1997;3:409-417.
24. Pflanz S, Timans JC, Cheung J, et al. IL-27, a heterodimeric cytokine composed of EBl3 and p28 protein, induces proliferation of naive CD4(+) T cells. Immunity. 2002;16:779-790.
25. Vilcek J. The cytokines: an overview. In: Thomson A, ed. The Cytokine Handbook. London, UK: Academic Press; 1998:1-20.
26. Kelso A. Cytokines: principles and prospects. Immunol Cell Biol. 1998;76:300-317.
27. Bazan JF. Unraveling the structure of IL-2. Science. 1992;257:410-413.
28. Boulay JL, Paul WE. The interleukin-4 family of lymphokines. Curr Opin Immunol. 1992;4:294-298.
29. Rothwell NJ, Luheshi GN. Interleukin 1 in the brain: biology, pathology and therapeutic target. Trends Neurosci. 2000;23:618-625.
30. Fantuzzi G, Dinarello CA. Interleukin-18 and interleukin-1 beta: two cytokine substrates for ICE (caspase-1). J Clin Immunol. 1999;19:1-11.
31. Smith DE, Renshaw BR, Ketchem RR, Kubin M, Garka KE, Sims JE. Four new members expand the interleukin-1 superfamily. J Biol Chem. 2000;275:1169-1175.
32. Bodmer JL, Schneider P, Tschopp J. The molecular architecture of the TNF superfamily. Trends Biochem Sci. 2002;27:19-26.
33. Janeway-CA, Travers P, Walport M, Shlomchik M. Immunobiology. 5th ed. New York, NY: Garland Publishing; 2001.
34. Fickenscher H, Hor S, Kupers H, Knappe A, Wittmann S, Sticht H. The interleukin-10 family of cytokines. Trends Immunol. 2002;23:89-96.
35. Gurling HM, Kalsi G, Brynjolfson J, et al. Genomewide genetic linkage analysis confirms the presence of susceptibility loci for schizophrenia, on chromosomes 1q32.2, 5q33.2, and 8p21-22 and provides support for linkage to schizophrenia, on chromosomes 11q23.3-24 and 20q12.1-11.23. Am J Hum Genet. 2001;68:661-673.
36. Rosa A, Fananas L, Cuesta MJ, Peralta V, Sham P. 1q21-q22 locus is associated with susceptibility to the reality-distortion syndrome of schizophrenia spectrum disorders. Am J Med Genet. 2002;114:516-518.
37. Brzustowicz LM, Hodgkinson KA, Chow EW, Honer WG, Bassett AS. Location of a major susceptibility locus for familial schizophrenia on chromosome 1q21-q22. Science. 2000;288:678-682.
38. Chiavetto LB, Boin F, Zanardini R, et al. Association between promoter polymorphic haplotypes of interleukin-10 gene and schizophrenia. Biol Psychiatry. 2002;51:480-484.
39. Katila H, Hanninen K, Hurme M. Polymorphisms of the interleukin-1 gene complex in schizophrenia. Mol Psychiatry. 1999;4:179-181.
40. Meisenzahl EM, Rujescu D, Kirner A, et al. Association of an interleukin-1 beta genetic polymorphism with altered brain structure in patients with schizophrenia. Am J Psychiatry. 2001;158:1316-1319.
41. Schwab SG, Hallmayer J, Albus M, et al. A genome-wide autosomal screen for schizophrenia susceptibility loci in 71 families with affected siblings: support for loci on chromosome 10p and 6. Mol Psychiatry. 2000;5:638-649.
42. Rioux JD, Daly MJ, Silverberg MS, et al. Genetic variation in the 5q31 cytokine gene cluster confers susceptibility to Crohn disease. Nat Genet. 2001;29:223-228.
43. Lindholm E, Ekholm B, Balciuniene J, et al. Linkage analysis of a large Swedish kindred provides further support for a susceptibility locus for schizophrenia on chromosome 6p23. Am J Med Genet. 1999;88:369-377.
44. Boin F, Zanardini R, Pioli R, Altamura CA, Maes M, Gennarelli M. Association between -G308A tumor necrosis factor alpha gene polymorphism and schizophrenia. Mol Psychiatry. 2001;6:79-82.
45. Riedel M, Kronig H, Schwarz MJ, et al. No association between the G308A polymorphism of the tumor necrosis factor-alpha gene and schizophrenia. Eur Arch Psychiatry Clin Neurosci. 2002;252:232-234.
46. Kwiatkowski DJ, Diaz MO. Dinucleotide repeat polymorphism at the IFNA locus (9p22). Hum Mol Genet. 1992;1:658.
47. Matusevicius D, Navikas V, Palasik W, Pirskanen R, Fredrikson S, Link H. Tumor necrosis factor-alpha, lymphotoxin, interleukin (IL)-6, IL-10, IL-12 and perforin mRNA expression in mononuclear cells in response to acetylcholine receptor is augmented in myasthenia gravis. J Neuroimmunol. 1996;71:191-198.
48. Yssel H, de Waal MR, Roncarolo MG, et al. IL-10 is produced by subsets of human CD4+ T cell clones and peripheral blood T cells. J Immunol. 1992;149:2378-2384.
49. Hayakawa S, Fujikawa T, Fukuoka H, et al. Murine fetal resorption and experimental pre-eclampsia are induced by both excessive Th1 and Th2 activation. J Reprod Immunol. 2000;47:121-138.
50. Seder RA, Paul WE. Acquisition of lymphokine-producing phenotype by CD4+ T cells. Annu Rev Immunol. 1994;12:635-673.
51. Romagnani S. Biology of human TH1 and TH2 cells. J Clin Immunol. 1995;15:121-129.
52. Paludan SR. Interleukin-4 and interferon-gamma: the quintessence of a mutual antagonistic relationship. Scand J Immunol. 1998;48:459-468.
53. Aloisi F, Ria F, Adorini L. Regulation of T-cell responses by CNS antigen-presenting cells: different roles for microglia and astrocytes. Immunol Today. 2000;21:141-147.
54. Ford AL, Foulcher E, Lemckert FA, Sedgwick JD. Microglia induce CD4 T lymphocyte final effector function and death. J Exp Med. 1996;184:1737-1745.
55. Kreutzberg GW. Microglia: a sensor for pathological events in the CNS. Trends Neurosci. 1996;19:312-318.
56. Krakowski ML, Owens T. The central nervous system environment controls effector CD4+ T cell cytokine profile in experimental allergic encephalomyelitis. Eur J Immunol. 1997;27:2840-2847.
57. Stalder AK, Pagenstecher A, Yu NC, et al. Lipopolysaccharide-induced IL-12 expression in the central nervous system and cultured astrocytes and microglia. J Immunol. 1997;159:1344-1351.
58. Hailer NP, Heppner FL, Haas D, Nitsch R. Astrocytic factors deactivate antigen presenting cells that invade the central nervous system. Brain Pathol. 1998;8:459-474.
59. Banks WA, Kastin AJ, Durham DA. Bidirectional transport of interleukin-1 alpha across the blood-brain barrier. Brain Res Bull. 1989;23:433-437.
60. Banks WA, Ortiz L, Plotkin SR, Kastin AJ. Human interleukin (IL) 1 alpha, murine IL-1 alpha and murine IL-1 beta are transported from blood to brain in the mouse by a shared saturable mechanism. J Pharmacol Exp Ther. 1991;259:988-996.
61. Bynks WA, Kastin AJ, Broadwell RD. Passage of cytokines across the blood-brain barrier. Neuroimmunomodulation. 1995;2:241-248.
62. Waguespack PJ, Banks WA, Kastin AJ. Interleukin-2 does not cross the blood-brain barrier by a saturable transport system. Brain Res Bull. 1994;34:103-109.
63. Maness LM, Kastin AJ, Banks WA. Relative contributions of a CVO and the microvascular bed to delivery of blood-borne IL-1alpha to the brain. Am J Physiol. 1998;275(2, pt 1):E207-E212.
64. Hashimoto M, Ishikawa Y, Yokota S, et al. Action site of circulating interleukin-1 on the rabbit brain. Brain Res. 1991;540:217-223.
65. Davson H, Segal MB. Physiology of the CSF and Blood-Brain Barriers. Boca Raton, Fla: CRC Press; 1996.
66. Ganong WF. Circumventricular organs: definition and role in the regulation of endocrine and autonomic function. Clin Exp Pharmacol Physiol. 2000;27:422-427.
67. Blatteis CM, Hales JR, McKinley MJ, Fawcett AA. Role of the anteroventral third ventricle region in fever in sheep. Can J Physiol Pharmacol. 1987;65:1255-1260.
68. Blatteis CM, Bealer SL, Hunter WS, Llanos Q, Ahokas RA, Mashburn TA Jr. Suppression of fever after lesions of the anteroventral third ventricle in guinea pigs. Brain Res Bull. 1983;11:519-526.
69. Lee SC, Dickson DW, Brosnan CF. Interleukin-1, nitric oxide and reactive astrocytes. Brain Behav Immunol. 1995;9:345-354.
70. Stitt JT. Evidence for the involvement of the organum vasculosum laminae terminalis in the febrile response of rabbits and rats. J Physiol. 1985;368:501-511.
71. Ericsson A, Arias C, Sawchenko PE. Evidence for an intramedullary prostaglandin-dependent mechanism in the activation of stress-related neuroendocrine circuitry by intravenous interleukin-1. J Neurosci. 1997;17:7166-7179.
72. Quan N, Herkenham M. Connecting cytokines and brain: a review of current issues. Histol Histopathol. 2002;17:273-288.
73. Watkins LR, Wiertelak EP, Goehler LE, Smith KP, Martin D, Maier SF. Characterization of cytokine-induced hyperalgesia. Brain Res. 1994;654:15-26.
74. Sehic E, Blatteis CM. Blockade of lipopolysaccharide-induced fever by subdiaphragmatic vagotomy in guinea pigs. Brain Res. 1996;726:160-166.
75. Fleshner M, Goehler LE, Hermann J, Relton JK, Maier SF, Watkins LR. Interleukin-1 beta induced corticosterone elevation and hypothalamic NE depletion is vagally mediated. Brain Res Bull. 1995;37:605-610.
76. Opp MR, Toth LA. Somnogenic and pyrogenic effects of interleukin-1beta and lipopolysaccharide in intact and vagotomized rats. Life Sci. 1998;62:923-936.
77. Bret-Dibat JL, Bluthe RM, Kent S, Kelley KW, Dantzer R. Lipopolysaccharide and interleukin-1 depress food-motivated behavior in mice by a vagal-mediated mechanism. Brain Behav Immunol. 1995;9:242-246.
78. Konsman JP, Parnet P, Dantzer R. Cytokine-induced sickness behaviour: mechanisms and implications. Trends Neurosci. 2002;25:154-159.
79. Quan N, Whiteside M, Herkenham M. Time course and localization patterns of interleukin-1 beta messenger RNA expression in brain and pituitary after peripheral administration of lipopolysaccharide. Neuroscience. 1998;83:281-293.
80. Vallieres L, Rivest S. Regulation of the genes encoding interleukin-6, its receptor, and gp130 in the rat brain in response to the immune activator lipopolysaccharide and the proinflammatory cytokine interleukin-1 beta. J Neurochem. 1997;69:1668-1683.
81. Nadeau S, Rivest S. Regulation of the gene encoding tumor necrosis factor alpha (TNF-alpha) in the rat brain and pituitary in response in different models of systemic immune challenge. J Neuropathol Exp Neurol. 1999;58:61-77.
82. Quan N, Sundar SK, Weiss JM. Induction of interleukin-1 in various brain regions after peripheral and central injections of lipopolysaccharide. J Neuroimmunol. 1994;49:125-134.
83. Ek M, Engblom D, Saha S, Blomqvist A, Jakobsson PJ, Ericsson-Dahlstrand A. Inflammatory response: pathway across the blood-brain barrier. Nature. 2001;410:430-431.
84. Mark KS, Trickler WJ, Miller DW. Tumor necrosis factor-alpha induces cyclooxygenase-2 expression and prostaglandin release in brain microvessel endothelial cells. J Pharmacol Exp Ther. 2001;297:1051-1058.
85. Johnson RW, von Borell E. Lipopolysaccharide-induced sickness behavior in pigs is inhibited by pretreatment with indomethacin. J Anim Sci. 1994;72:309-314.
86. Dunn AJ, Swiergiel AH. The role of cyclooxygenases in endotoxin- and interleukin-1-induced hypophagia. Brain Behav Immunol. 2000;14:141-152.
87. Oehmichen M, Domasch D, Wietholter H. Origin, proliferation, and fate of cerebrospinal fluid cells. A review on cerebrospinal fluid cell kinetics. J Neurol. 1982;227:145-150.
88. Hickey WF. Migration of hematogenous cells through the blood-brain barrier and the initiation of CNS inflammation. Brain Pathol. 1991;1:97-105.
89. Frei K, Piani D, Pfister HW, Fontana A. Immune-mediated injury in bacterial meningitis. Int Rev Exp Pathol. 1993;34(Pt B):183-192.
90. Del Maschio A, De Luigi A, Martin-Padura I, et al. Leukocyte recruitment in the cerebrospinal fluid of mice with experimental meningitis is inhibited by an antibody to junctional adhesion molecule (JAM). J Exp Med. 1999;190:1351-1356.
91. Bienvenu J, Monneret G, Fabien N, Revillard JP. The clinical usefulness of the measurement of cytokines. Clin Chem Lab Med. 2000;38:267-285.
92. Bakhiet M, Tjernlund A, Mousa A, et al. RANTES promotes growth and survival of human first-trimester forebrain astrocytes. Nat Cell Biol. 2001;3:150-157.
93. Vankelecom H, Matthys P, Denef C. Involvement of nitric oxide in the interferon-gamma-induced inhibition of growth hormone and prolactin secretion in anterior pituitary cell cultures. Mol Cell Endocrinol. 1997;129:157-167.
94. Kamata M, Higuchi H, Yoshimoto M, Yoshida K, Shimizu T. Effect of single intracerebroventricular injection of alpha-interferon on monoamine concentrations in the rat brain. Eur Neuropsychopharmacol. 2000;10:129-132.
95. Morikawa O, Sakai N, Obara H, Saito N. Effects of interferon-alpha, interferon-gamma and cAMP on the transcriptional regulation of the serotonin transporter. Eur J Pharmacol. 1998;349:317-324.
96. Shuto H, Kataoka Y, Horikawa T, Fujihara N, Oishi R. Repeated interferon-alpha administration inhibits dopaminergic neural activity in the mouse brain. Brain Res. 1997;747:348-351.
97. Katafuchi T, Take S, Hori T. Roles of cytokines in the neural-immune interactions: modulation of NMDA responses by IFN-alpha. Neurobiology (Bp). 1995;3:319-327.
98. Nickola TJ, Ignatowski TA, Reynolds JL, Spengler RN. Antidepressant drug-induced alterations in neuron-localized tumor necrosis factor-alpha mRNA and alpha(2)-adrenergic receptor sensitivity. J Pharmacol Exp Ther. 2001;297:680-687.
99. Ando T, Dunn AJ. Mouse tumor necrosis factor-alpha increases brain tryptophan concentrations and norepinephrine metabolism while activating the HPA axis in mice. Neuroimmunomodulation. 1999;6:319-329.
100. Hayley S, Wall P, Anisman H. Sensitization to the neuroendocrine, central monoamine and behavioural effects of murine tumor necrosis factor-alpha: peripheral and central mechanisms. Eur J Neurosci. 2002;15:1061-1076.
101. Ramamoorthy S, Ramamoorthy JD, Prasad PD, et al. Regulation of the human serotonin transporter by interleukin-1 beta. Biochem Biophys Res Commun. 1995;216:560-567.
102. Gemma C, Imeri L, De Simoni MG, Mancia M. Interleukin-1 induces changes in sleep, brain temperature, and serotonergic metabolism. Am J Physiol. 1997;272(2, Pt 2): R601-R606.
103. Imeri L, Gemma C, De Simoni MG, Opp MR, Mancia M. Hypothalamic serotonergic activity correlates better with brain temperature than with sleep-wake cycle and muscle tone in rats. Neuroscience. 1999;89:1241-1246.
104. Opp MR, Smith EM, Hughes TK Jr. Interleukin-10 (cytokine synthesis inhibitory factor) acts in the central nervous system of rats to reduce sleep. J Neuroimmunol. 1995;60:165-168.
105. Petitto JM, McCarthy DB, Rinker CM, Huang Z, Getty T. Modulation of behavioral and neurochemical measures of forebrain dopamine function in mice by species-specific interleukin-2. J Neuroimmunol. 1997;73:183-190.
106. Hanisch UK, Quirion R. Interleukin-2 as a neuroregulatory cytokine. Brain Res Brain Res Rev. 1995;21:246-284.
107. Van Wagoner NJ, Benveniste EN. Interleukin-6 expression and regulation in astrocytes. J Neuroimmunol. 1999;100:124-139.
108. Gadient RA, Otten UH. Interleukin-6 (IL-6) - a molecule with both beneficial and destructive potentials. Prog Neurobiol. 1997;52:379-390.
109. Song C, Merali Z, Anisman H. Variations of nucleus accumbens dopamine and serotonin following systemic interleukin-1, interleukin-2 or interleukin-6 treatment. Neuroscience. 1999;88:823-836.
110. Qiu Z, Parsons KL, Gruol DL. Interleukin-6 selectively enhances the intracellular calcium response to NMDA in developing CN5 neurons. J Neurosci. 1995;15:6688-6699.
111. Qiu Z, Sweeney DD, Netzeband JG, Gruol DL. Chronic interleukin-6 alters NMDA receptor-mediated membrane responses and enhances neurotoxicity in developing CNS neurons. J Neurosci. 1998;18:10445-10456.
112. Wang J, Dunn AJ. The role of interleukin-6 in the activation of the hypothalamo-pituitary-adrenocortical axis and brain indoleamines by endotoxin and interleukin-1 beta. Brain Res. 1999;815:337-348.
113. Wang J, Dunn AJ. Mouse interleukin-6 stimulates the HPA axis and increases brain tryptophan and serotonin metabolism. Neurochem Int. 1998;33:143-154.
114. Zalcman S, Green-Johnson JM, Murray L, et al. Cytokine-specific central monoamine alterations induced by interleukin-1, -2 and -6. Brain Res. 1994;643:40-49.
115. Barkhudaryan N, Dunn AJ. Molecular mechanisms of actions of interleukin-6 on the brain, with special reference to serotonin and the hypothalamo-pituitary-adrenocortical axis. Neurochem Res. 1999;24:1169-1180.
116. Katsuki H, Nakai S, Hirai Y, Akaji K, Kiso Y, Satoh M. Interleukin-1 beta inhibits long-term potentiation in the CA3 region of mouse hippocampal slices. Eur J Pharmacol. 1990;181:323-326.
117. Bellinger FP, Madamba S, Siggins GR. Interleukin 1 beta inhibits synaptic strength and long-term potentiation in the rat CA1 hippocampus. Brain Res. 1993;628:227-234.
118. Beattie EC, Stellwagen D, Morishita W, et al. Control of synaptic strength by glial TNFalpha. Science. 2002;295:2282-2285.
119. Gibertini M. Cytokines and cognitive behavior. Neuroimmunomodulation. 1998;5:160-165.
120. Gibertini M, Newton C, Friedman H, Klein TW. Spatial learning impairment in mice infected with Legionelia pneumophila or administered exogenous interleukin-1-beta. Brain Behav Immunol. 1995;9:113-128.
121. Mellor AL, Munn DH. Tryptophan catabolism and T-cell tolerance: immunosuppression by starvation? Immunol Today. 1999;20:469-473.
122. Munn DH, Shafizadeh E, Attwood JT, Bondarev I, Pashine A, Mellor AL. Inhibition of T cell proliferation by macrophage tryptophan catabolism. J Exp Med. 1999;189:1363-1372.
123. Weiss G, Murr C, Zoller H, et al. Modulation of neopterin formation and tryptophan degradation by Th1- and Th2-derived cytokines in human monocytic cells. Clin Exp Immunol. 1999;116:435-440.
124. Alberati GD, Ricciardi CP, Kohler C, Cesura AM. Regulation of the kynurenine metabolic pathway by interferon-gamma in murine cloned macrophages and microglial cells. J Neurochem. 1996;66:996-1004.
125. Farrar WL, Kilian PL, Ruff MR, Hill JM, Pert CB. Visualization and characterization of interleukin 1 receptors in brain. J Immunol. 1987;139:459-463.
126. Breder CD, Dinarello CA, Saper CB. Interleukin-1 immunoreactive innervation of the human hypothalamus. Science. 1988;240:321-324.
127. Tazi A, Dantzer R, Crestani F, Le Moal M. Interleukin-1 induces conditioned taste aversion in rats: a possible explanation for its pituitary-adrenal stimulating activity. Brain Res. 1988;473:369-371.
128. Plata-Salaman CR, Oomura Y, Kai Y. Tumor necrosis factor and interleukin-1 beta: suppression of food intake by direct action in the central nervous system. Brain Res. 1988;448:106-114.
129. Van Dam AM, Brouns M, Louisse S, Berkenbosch F. Appearance of interleukin-1 in macrophages and in ramified microglia in the brain of endotoxin-treated rats: a pathway for the induction of non-specific symptoms of sickness? Brain Res. 1992;588:291-296.
130. Gatti S, Bartfai T. Induction of tumor necrosis factor-alpha mRNA in the brain after peripheral endotoxin treatment: comparison with interleukin-1 family and interleukin-6. Brain Res. 1993;624:291-294.
131. Laye S, Parnet P, Goujon E, Dantzer R. Peripheral administration of lipopolysaccharide induces the expression-of cytokine transcripts in the brain and pituitary of mice. Brain Res Mol Brain Res. 1994;27:157-162.
132. Dantzer R. Cytokine-induced sickness behavior: where do we stand? Brain Behav Immunol. 2001;15:7-24.
133. Papanicolaou DA, Wilder RL, Manolagas SC, Chrousos GP. The pathophysiologic roles of interleukin-6 in human disease. Ann Intern Med. 1998;128:127-137.
134. Schaefer M, Engelbrecht MA, Gut O, et al. Interferon alpha (IFNalpha) and psychiatric syndromes: a review. Prog Neuropsychopharmacol Biol Psychiatry. 2002;26:731-746.
135. Capuron L, Ravaud A, Neveu PJ, Miller AH, Maes M, Dantzer R. Association between decreased serum tryptophan concentrations and depressive symptoms in cancer patients undergoing cytokine therapy. Mol Psychiatry. 2002;7:468-473.
136. Lerner DM, Stoudemire A, Rosenstein DL. Neuropsychiatric toxicity associated with cytokine therapies. Psychosomatics. 1999;40:428-435.
137. Fattovich G, Giustina G, Favarato S, Ruol A. A survey of adverse events in 11 241 patients with chronic viral hepatitis treated with alfa interferon. J Hepatol. 1996;24:38-47.
138. Denicoff KD, Rubinow DR, Papa MZ, et al. The neuropsychiatric effects of treatment with interleukin-2 and lymphokine-activated killer cells. Ann Intern Med. 1987;107:293-300.
139. Reichenberg A, Yirmiya R, Schuld A, et al. Cytokine-associated emotional and cognitive disturbances in humans. Arch Gen Psychiatry. 2001;58:445-452.
140. Seidel A, Arolt V, Hunstiger M, Rink L, Behnisch A, Kirchner H. Increased CD56+ natural killer cells and related cytokines in major depression. Clin Immunol Immunopathol. 1996;78:83-85.
141. Maes M, Scharpe S, Meltzer HY, et al. Increased neopterin and interferon-gamma secretion and lower availability of L-tryptophan in major depression: further evidence for an immune response. Psychiatry Res. 1994;54:143-160.
142. Maes M, Verkerk R, Vandoolaeghe E, et al. Serotonin-immune interactions in major depression: lower serum tryptophan as a marker of an immune-inflammatory response. Eur Arch Psychiatry Clin Neurosci. 1997;247:154-161.
143. Maes M, Song C, Lin AH, et al. Negative immunoregulatory effects of antidepressants: inhibition of interferon-gamma and stimulation of interleukin-10 secretion. Neuropsychopharmacology. 1999;20:370-379.
144. Mohr DC, Goodkin DE, Islar J, Hauser SL, Genain CP. Treatment of depression is associated with suppression of nonspecific and antigen-specific T(H)1 responses in multiple sclerosis. Arch Neurol. 2001;58:1081-1086.
145. Maes M, Scharpe S, Meltzer HY, et al. Relationships between interleukin-6 activity, acute phase proteins, and function of the hypothalamic-pituitary-adrenal axis in severe depression. Psychiatry Res. 1993;49:11-27.
146. Maes M, Meltzer HY, Bosmans E, et al. Increased plasma concentrations of interleukin-6, soluble interleukin-6, soluble interleukin-2 and transferrin receptor in major depression. J Affect Disord. 1995;34:301-309.
147. Sluzewska A, Rybakowski J, Bosmans E, et al. Indicators of immune activation in major depression, Psychiatry Res. 1996;64:161-167.
148. Berk M, Wadee AA, Kuschke RH, O'Neill KA. Acute phase proteins in major depression. J Psychosom Res. 1997;43:529-534.
149. Maes M, Bosmans E, De Jongh R, Kenis G, Vandoolaeghe E, Neels H. Increased serum IL-6 and IL-1 receptor antagonist concentrations in major depression and treatment-resistant depression. Cytokine. 1997;9:853-858.
150. Frommberger UH, Bauer J, Haselbauer P, Fraulin A, Riemann D, Berger M. Interleukin-6 (IL-6) plasma levels in depression and schizophrenia: comparison between the acute state and after remission. Eur Arch Psychiatry Clin Neurosci. 1997;247:228-233.
151. Song C, Lin A, Bonaccorso S, et al. The inflammatory response system and the availability of plasma tryptophan in patients with primary sleep disorders and major depression. J Affect Disord. 1998;49:211-219.
152. Smith RS, Maes M. The macrophage-T-lymphocyte theory of schizophrenia: additional evidence. Med Hypotheses. 1995;45:135-141.
153. Plata-Salaman CR. Immunoregulators in the nervous system. Neurosci Biobehav Rev. 1991;15:185-215.
154. Roy A, Pickar D, Paul S, Doran A, Chrousos GP, Gold PW. CSF corticotropin-releasing hormone in depressed patients and normal control subjects. Am J Psychiatry. 1987;144:641-645.
155. Salas MA, Evans SW, Levell MJ, Whicher JT. Interleukin-6 and ACTH act synergistically to stimulate the release of corticosterone from adrenal gland cells. Clin Exp Immunol. 1990;79:470-473.
156. LeMay LG, Vander AJ, Kluger MJ. The effects of psychological stress on plasma interleukin-6 activity in rats. Physiol Behav. 1990;47:957-961.
157. Zhou D, Kusnecov AW, Shurin MR, DePaoli M, Rabin BS. Exposure to physical and psychological stressors elevates plasma interleukin 6: relationship to the activation of hypothalamic-pituitary-adrenal axis. Endocrinology. 1993;133:2523-2530.
158. Miyahara S, Komori T, Fujiwara R, et al. Effects of repeated stress on expression of interleukin-6 (IL-6) and IL-6 receptor mRNAs in rat hypothalamus and midbrain. Life Sci. 2000;66:L93-L98.
159. Rothermundt M, Arolt V, Fenker J, Gutbrodt H, Peters M, Kirchner H. Different immune patterns in melancholic and non-melancholic major depression. Eur Arch Psychiatry Clin Neurosci. 2001;251:90-97.
160. Licinio J, Seibyl JP, Altemus M, Charney DS, Krystal JH. Elevated CSF levels of interleukin-2 in neuroleptic-free schizophrenic patients. Am J Psychiatry. 1993;150:1408-1410.
161. McAllister CG, van Kammen DP, Rehn TJ, et al. Increases in CSF levels of interleukin-2 in schizophrenia: effects of recurrence of psychosis and medication status. Am J Psychiatry. 1995;152:1291-1297.
162. Rapaport MH, McAllister CG, Pickar D, Tamarkin L, Kirch DG, Paul SM. CSF IL-1 and IL-2 in medicated schizophrenic patients and normal volunteers. Schizophr Res. 1997;25:123-129.
163. Barak V, Barak Y, Levine J, Nisman B, Roisman I. Changes in interleukin-1 beta and soluble interleukin-2 receptor levels in CSF and serum of schizophrenic patients. J Basic Clin Physiol Pharmacol. 1995;6:61-69.
164. el Mallakh RS, Suddath RL, Wyatt RJ. Interleukin-1 alpha and interleukin-2 in cerebrospinal fluid of schizophrenic subjects. Prog Neuropsychopharmacol Biol Psychiatry. 1993;17:383-391.
165. Mittleman BB, Castellanos FX, Jacobsen LK, Rapoport JL, Swedo SE, Shearer GM. Cerebrospinal fluid cytokines in pediatric neuropsychiatric disease. J Immunol. 1997;159:2994-2999.
166. Kim YK, Kim L, Lee MS. Relationships between interleukins, neurotransmitters and psychopathology in drug-free male schizophrenics. Schizophr Res. 2000;44:165-175.
167. Theodoropoulou St, Spanakos G, Baxevanis CN, et al. Cytokine serum levels, autologous mixed lymphocyte reaction and surface marker analysis in never medicated and chronically medicated schizophrenic patients. Schizophr Res. 2001;47:12-25.
168. Arolt V, Rothermundt M, Wandinger KP, Kirchner H. Decreased in vitro production of interferon-gamma and interleukin-2 in whole blood of patients with schizophrenia during treatment. Mol Psychiatry. 2000;5:150-158.
169. Kim YK, Lee MS, Suh KY. Decreased interleukin-2 production in Korean schizophrenic patients. Biol Psychiatry. 1998;43:701-704.
170. Ganguli R, Brar JS, Solomon W, Chengappa KN, Rabin BS. Altered interleukin-2 production in schizophrenia: association between clinical state and autoantibody production. Psychiatry Res 1992;44:113-123.
171. Yang ZW, Chengappa KN, Shurin G, et al. An association between anti-hippocampal antibody concentration and lymphocyte production of IL-2 in patients with schizophrenia. Psychol Med. 1994;24:449-455.
172. Ganguli R, Brar JS, Chengappa KR, et al. Mitogen-stimulated interleukin-2 production in never-medicated, first-episode schizophrenic patients. The influence of age at onset and negative symptoms [see comments]. Arch Gen Psychiatry. 1995;S2:668-672.
173. O'Donnell MC, Catts SV, Ward PB, et al. Increased production of interleukin-2 (IL-2) but not soluble interleukin-2 receptors (sIL-2R) in unmedicated patients with schizophrenia and schizophreniform disorder. Psychiatry Res. 1996;65:171-178.
174. Cazzullo CL, Sacchetti E, Galluzzo A, et al. Cytokine profiles in drug-naive schizophrenic patients. Schizophr Res. 2001;47:293-298.
175. Hornberg M, Arolt V, Wilke I, Kruse A, Kirchner H. Production of interferons and lymphokines in leukocyte cultures of patients with schizophrenia. Schizophr Res. 1995;15:237-242.
176. Wilke I, Arolt V, Rothermundt M, Weitzsch C, Hornberg M, Kirchner H. Investigations of cytokine production in whole blood cultures of paranoid and residual schizophrenic patients. Eur Arch Psychiatry Clin Neurosci. 1996;246:279-284.
177. Song C, Lin A, Kenis G, Bosmans E, Maes M. Immunosuppressive effects of clozapine and haloperidol: enhanced production of the interleukin-1 receptor antagonist. Schizophr Res. 2000;42:157-164.
178. Maes M, Bocchio CL, Bignotti S, et al. 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. 2002;54:281-291.
179. Rothermundt M, Arolt V, Weitzsch C, Eckhoff D, Kirchner H. Immunological dysfunction in schizophrenia: a systematic approach. Neuropsychobiology. 1998;37:186-193.
180. Cazzullo CL, Scarone S, Grassi B, et al. Cytokine production in chronic schizophrenia patients with or without paranoid behaviour. Prog Neuropsychopharmacol Biol Psychiatry. 1998;22:947-957.
181. Ringheim GE, Burgher KL, Heroux JA. Interleukin-6 mRNA expression by cortical neurons in culture: evidence for neuronal sources of interleukin-6 production in the brain. J Neuroimmunol. 1995;63:113-123.
182. Ganguli R, Yang Z, Shurin G, et al. Serum interleukin-6 concentration in schizophrenia: elevation associated with duration of illness. Psychiatry Res. 1994;51:1-10.
183. Maes M, Bosmans E, Calabrese J, Smith R, Meltzer HY. Interleukin-2 and interleukin-6 in schizophrenia and mania: effects of neuroleptics and mood stabilizers. J Psychiatr Res. 1995;29:141-152.
184. Naudin J, Mege JL, Azorin JM, Dassa D. Elevated circulating levels of IL-6 in schizophrenia. Schizophr Res. 1996;20:269-273.
185. Lin A, Kenis G, Bignotti S, et al. The inflammatory response system in treatment-resistant schizophrenia: increased serum interleukin-6. Schizophr Res. 1998;32:9-15.
186. Akiyama K. Serum levels of soluble IL-2 receptor alpha, IL-6 and IL-1 receptor antagonist in schizophrenia before and during neuroleptic administration. Schizophr Res. 1999;37:97-106.
187. Maes M, Bocchio CL, Bignotti S, et al. Effects of atypical antipsychotics on the inflammatory response system in schizophrenic patients resistant to treatment with typical neuroleptics. Eur Neuropsychopharmacol. 2000;10:119-124.
188. Haack M, Hinze SD, Fenzel T, et al. Plasma levels of cytokines and soluble cytokine receptors in psychiatric patients upon hospital admission: effects of confounding factors and diagnosis. J Psychiatr Res. 1999;33:407-418.
189. Maes M, Bosmans E, Kenis G, De Jong R, Smith RS, Meltzer HY. In vivo immunomodulatory effects of clozapine in schizophrenia. Schizophr Res. 1997;26:221-225.
190. Schwarz MJ, Chiang S, Müller N, Ackenheil M. T-helper-1 and T-helper-2 responses in psychiatric disorders. Brain Behav Immunol. 2001;15: 340-370.
191. Schwarz MJ, Muller N, Riedel M, Ackenheil M. The Th2-hypothesis of schizophrenia: a strategy to identify a subgroup of schizophrenia caused by immune mechanisms. Med Hypotheses. 2001;56:483-486.
192. Nawa H, Takahashi M, Patterson PH. Cytokine and growth factor involvement in schizophrenia - support for the developmental model. Mol Psychiatry. 2000;5:594-603.
193. The American College of Rheumatology nomenclature and case definitions for neuropsychiatric lupus syndromes. Arthritis Rheum. 1999;42:599-608.
194. Müller N, Riedel M, Scheppach C, et al. Beneficial antipsychotic effects of celecoxib add-on therapy compared to risperidone alone in schizophrenia. Am J Psychiatry. 2002;159:1029-1034.