Circulating tumour necrosis factor is highly correlated with brainstem serotonin transporter availability in humans

Brain, Behavior, and Immunity

Volumn 51, Issue , 2016, Pages 29-38

  Krishnadas, Rajeev ^a   Nicol, Alice ^b   Sassarini, Jen ^a   Puri, Navesh ^a   Burden, A David ^c   Leman, Joyce ^c   Combet, Emilie ^a   Pimlott, Sally ^d   Hadley, Donald ^b   McInnes, Iain B ^a   Cavanagh, Jonathan ^a  

^a UNIVERSITY OF GLASGOW   (United Kingdom)

^b SOUTHERN GENERAL HOSPITAL   (United Kingdom)

^c WESTERN INFIRMARY   (United Kingdom)

^d NHS GREATER GLASGOW AND CLYDE   (United Kingdom)

Author keywords

Cytokines; Depression; Inflammation; Serotonin transporter; SPECT; Tumor necrosis factor

Indexed keywords

CYTOKINE; ETANERCEPT; IODINE 123; METHOTREXATE; SEROTONIN TRANSPORTER; TUMOR NECROSIS FACTOR; SLC6A4 PROTEIN, HUMAN;

ADULT; AGED; ARTICLE; BIOAVAILABILITY; BRAIN STEM; CLINICAL ARTICLE; CONTROLLED STUDY; CORRELATIONAL STUDY; DISEASE ASSOCIATION; DRUG EFFECT; DRUG EFFICACY; FEMALE; HUMAN; MAJOR DEPRESSION; MALE; PRIORITY JOURNAL; PSORIATIC ARTHRITIS; SINGLE PHOTON EMISSION COMPUTED TOMOGRAPHY; TREATMENT OUTCOME; ANTAGONISTS AND INHIBITORS; BLOOD; DEPRESSION; DIAGNOSTIC IMAGING; METABOLISM; MIDDLE AGED;

ARTHRITIS, PSORIATIC; BRAIN STEM; DEPRESSION; ETANERCEPT; FEMALE; HUMANS; MIDDLE AGED; SEROTONIN PLASMA MEMBRANE TRANSPORT PROTEINS; TOMOGRAPHY, EMISSION-COMPUTED, SINGLE-PHOTON; TUMOR NECROSIS FACTOR-ALPHA;

EID: 84939817801     PISSN: 08891591     EISSN: 10902139     Source Type: Journal    
DOI: 10.1016/j.bbi.2015.08.005     Document Type: Article

References (94)

1. Albert, P.R., Benkelfat, C., The neurobiology of depression-revisiting the serotonin hypothesis. II. Genetic, epigenetic and clinical studies. Philos. Trans. R. Soc. Lond. B Biol. Sci., 368, 2013, 20120535.
2. Albert, P.R., Benkelfat, C., Descarries, L., The neurobiology of depression-revisiting the serotonin hypothesis. I. Cellular and molecular mechanisms. Philos. Trans. R. Soc. Lond. B Biol. Sci. 367 (2012), 2378–2381.
3. Baganz, N.L., Blakely, R.D., A dialogue between the immune system and brain, spoken in the language of serotonin. ACS Chem. Neurosci. 4 (2013), 48–63.
4. 123I]beta-CIT) in non-human primates: pharmacokinetics, biodistribution and SPECT brain imaging coregistered with MRI. Nucl. Med. Biol. 20 (1993), 597–606.
5. Beck, A.T., Steer, R.A., Ball, R., Ranieri, W., Comparison of Beck Depression Inventories -IA and -II in psychiatric outpatients. J. Pers. Assess. 67 (1996), 588–597.
6. Beygi, S., Lajevardi, V., Abedini, R., C-reactive protein in psoriasis: a review of the literature. J. Eur. Acad. Dermatol. Venereol., 2013.
7. Bhatia, A., Kast, R.E., Tumor necrosis factor (TNF) can paradoxically increase on etanercept treatment, occasionally contributing to TNF-mediated disease. J. Rheumatol. 34 (2007), 447–449 (author reply 449–450).
8. Brydon, L., Harrison, N.A., Walker, C., Steptoe, A., Critchley, H.D., Peripheral inflammation is associated with altered substantia nigra activity and psychomotor slowing in humans. Biol. Psychiatry 63 (2008), 1022–1029.
9. Canli, T., Lesch, K.-P., Long story short: the serotonin transporter in emotion regulation and social cognition. Nat. Neurosci. 10 (2007), 1103–1109.
10. Capuron, L., Miller, A.H., Immune system to brain signaling: neuropsychopharmacological implications. Pharmacol. Ther. 130 (2011), 226–238.
11. Capuron, L., Pagnoni, G., Drake, D.F., Woolwine, B.J., Spivey, J.R., Crowe, R.J., Votaw, J.R., Goodman, M.M., Miller, A.H., Dopaminergic mechanisms of reduced basal ganglia responses to hedonic reward during interferon alfa administration. Arch. Gen. Psychiatry 69 (2012), 1044–1053.
12. Cavanagh, J., Patterson, J., Pimlott, S., Dewar, D., Eersels, J., Dempsey, M.F., Wyper, D., Serotonin transporter residual availability during long-term antidepressant therapy does not differentiate responder and nonresponder unipolar patients. Biol. Psychiatry 59 (2006), 301–308.
13. Cavanagh, J., Paterson, C., McLean, J., Pimlott, S., McDonald, M., Patterson, J., Wyper, D., McInnes, I., Tumour necrosis factor blockade mediates altered serotonin transporter availability in rheumatoid arthritis: a clinical, proof-of-concept study. Ann. Rheum. Dis. 69 (2010), 1251–1252.
14. Coimbra, S., Oliveira, H., Reis, F., Belo, L., Rocha, S., Quintanilha, A., Figueiredo, A., Teixeira, F., Castro, E., Rocha-Pereira, P., Santos-Silva, A., C-reactive protein and leucocyte activation in psoriasis vulgaris according to severity and therapy. J. Eur. Acad. Dermatol. Venereol. 24 (2009), 789–796.
15. Coimbra, S., Figueiredo, A., Castro, E., Rocha-Pereira, P., Santos-Silva, A., The roles of cells and cytokines in the pathogenesis of psoriasis. Int. J. Dermatol. 51 (2012), 389–398.
16. Cools, R., Roberts, A.C., Robbins, T.W., Serotoninergic regulation of emotional and behavioural control processes. Trends Cogn. Sci. 12 (2008), 31–40.
17. Couch, Y., Anthony, D.C., Dolgov, O., Revischin, A., Festoff, B., Santos, A.I., Steinbusch, H.W., Strekalova, T., Microglial activation, increased TNF and SERT expression in the prefrontal cortex define stress-altered behaviour in mice susceptible to anhedonia. Brain Behav. Immun. 29 (2013), 136–146.
18. Critchley, H.D., Harrison, N.A., Visceral influences on brain and behavior. Neuron 77 (2013), 624–638.
19. Dantzer, R., O'Connor, J.C., Freund, G.G., Johnson, R.W., Kelley, K.W., From inflammation to sickness and depression: when the immune system subjugates the brain. Nat. Rev. Neurosci. 9 (2008), 46–56.
20. 123)I]beta-CIT SPECT to assess serotonin transporters in vivo in humans: a double-blind, placebo-controlled, crossover study with the selective serotonin reuptake inhibitor citalopram. Neuropsychopharmacology 30 (2005), 996–1005.
21. 123I]β-CIT SPECT to assess serotonin transporters in vivo in humans: a double-blind, placebo-controlled, crossover study with the selective serotonin reuptake inhibitor citalopram. Neuropsychopharmacology 30 (2005), 996–1005.
22. Descarries, L., Riad, M., Parent, M., Ultrastructure of the serotonin innervation in the mammalian central nervous system. Muller, C.P., Jacobs, B., (eds.) Handbook of Behavioural Neurobiology of Serotonin, 2010, Elsevier B.V., 65–101.
23. 3H]paroxetine binding and serotonin content of rat and rabbit cortical areas, hippocampus, neostriatum, ventral mesencephalic tegmentum, and midbrain raphe nuclei region. Synapse 9 (1991), 14–26.
24. Dowlati, Y., Herrmann, N., Swardfager, W., Liu, H., Sham, L., Reim, E.K., Lanctot, K.L., A meta-analysis of cytokines in major depression. Biol. Psychiatry 67 (2010), 446–457.
25. Ellison, V.J., Mocatta, T.J., Winterbourn, C.C., Darlow, B.A., Volpe, J.J., Inder, T.E., The relationship of CSF and plasma cytokine levels to cerebral white matter injury in the premature newborn. Pediatr. Res. 57 (2005), 282–286.
26. Fantuzzi, F., Del Giglio, M., Gisondi, P., Girolomoni, G., Targeting tumor necrosis factor alpha in psoriasis and psoriatic arthritis. Expert Opin. Ther. Targets 12 (2008), 1085–1096.
27. Feldmann, M., Maini, R.N., Anti-TNF alpha therapy of rheumatoid arthritis: what have we learned?. Annu. Rev. Immunol., 19, 2001.
28. Feldmann, M., Maini, R.N., TNF defined as a therapeutic target for rheumatoid arthritis and autoimmune diseases. Nat. Med. 9 (2003), 1245–1250.
29. Feldmann, M., Maini, R.N., Anti-TNF therapy, from rationale to standard of care: what lessons has it taught us?. J. Immunol. 185 (2010), 791–794.
30. Feldmann, M., Williams, R.O., Paleolog, E., What have we learnt from targeted anti-TNF therapy?. Ann. Rheum. Dis. 69:Suppl. 1 (2010), i97–i99.
31. Felger, J.C., Mun, J., Kimmel, H.L., Nye, J.A., Drake, D.F., Hernandez, C.R., Freeman, A.A., Rye, D.B., Goodman, M.M., Howell, L.L., Miller, A.H., Chronic interferon-alpha decreases dopamine 2 receptor binding and striatal dopamine release in association with anhedonia-like behavior in nonhuman primates. Neuropsychopharmacology 38 (2013), 2179–2187.
32. Gelfand, J.M., Kimball, A.B., Mostow, E.N., Chiou, C.F., Patel, V., Xia, H.A., Freundlich, B., Stevens, S.R., Patient-reported outcomes and health-care resource utilization in patients with psoriasis treated with etanercept: continuous versus interrupted treatment. Value Health 11 (2008), 400–407.
33. Gladman, D.D., Antoni, C., Mease, P., Clegg, D.O., Nash, P., Psoriatic arthritis: epidemiology, clinical features, course, and outcome. Ann. Rheum. Dis. 64:Suppl. 2 (2005), ii14–ii17.
34. Gryglewski, G., Lanzenberger, R., Kranz, G.S., Cumming, P., Meta-analysis of molecular imaging of serotonin transporters in major depression. J. Cereb. Blood Flow Metab. 34 (2014), 1096–1103.
35. Hannestad, J., Gallezot, J.D., Schafbauer, T., Lim, K., Kloczynski, T., Morris, E.D., Carson, R.E., Ding, Y.S., Cosgrove, K.P., Endotoxin-induced systemic inflammation activates microglia: [(1)(1)C]PBR28 positron emission tomography in nonhuman primates. Neuroimage 63 (2012), 232–239.
36. Hannestad, J., Subramanyam, K., Dellagioia, N., Planeta-Wilson, B., Weinzimmer, D., Pittman, B., Carson, R.E., Glucose metabolism in the insula and cingulate is affected by systemic inflammation in humans. J. Nucl. Med. 53 (2012), 601–607.
37. Hannestad, J., DellaGioia, N., Gallezot, J.D., Lim, K., Nabulsi, N., Esterlis, I., Pittman, B., Lee, J.Y., O'Connor, K.C., Pelletier, D., Carson, R.E., The neuroinflammation marker translocator protein is not elevated in individuals with mild-to-moderate depression: a [(1)(1)C]PBR28 PET study. Brain Behav. Immun. 33 (2013), 131–138.
38. Harrison, N.A., Brydon, L., Walker, C., Gray, M.A., Steptoe, A., Critchley, H.D., Inflammation causes mood changes through alterations in subgenual cingulate activity and mesolimbic connectivity. Biol. Psychiatry 66 (2009), 407–414.
39. Harrison, N.A., Brydon, L., Walker, C., Gray, M.A., Steptoe, A., Dolan, R.J., Critchley, H.D., Neural origins of human sickness in interoceptive responses to inflammation. Biol. Psychiatry 66 (2009), 415–422.
40. Hayes, J., Koo, J., Psoriasis: depression, anxiety, smoking and drinking habits. Dermatol. Ther. 23 (2010), 174–180.
41. Hornung, J.-P., The human raphe nuclei and the serotonergic system. J. Chem. Neuroanat. 26 (2003), 331–343.
42. Hornung, R., Reed, L., Estimation of average concentration in the presence of nondetectable values. Appl. Occup. Environ. Hyg. 5 (1990), 46–51.
43. Howerton, A.R., Roland, A.V., Bale, T.L., Dorsal raphe neuroinflammation promotes dramatic behavioral stress dysregulation. J. Neurosci. 34 (2014), 7113–7123.
44. Howren, M.B., Lamkin, D.M., Suls, J., Associations of depression with C-reactive protein, IL-1, and IL-6: a meta-analysis. Psychosom. Med. 71 (2009), 171–186.
45. IBMCorp, SPSS Statistics for Windows. 2011, IBM Corp, Armonk, New York.
46. Innis, R.B., Cunningham, V.J., Delforge, J., Fujita, M., Gjedde, A., Gunn, R.N., Holden, J., Houle, S., Huang, S.-C., Ichise, M., Iida, H., Ito, H., Kimura, Y., Koeppe, R.A., Knudsen, G.M., Knuuti, J., Lammertsma, A.A., Laruelle, M., Logan, J., Maguire, R.P., Mintun, M.A., Morris, E.D., Parsey, R., Price, J.C., Slifstein, M., Sossi, V., Suhara, T., Votaw, J.R., Wong, D.F., Carson, R.E., Consensus nomenclature for in vivo imaging of reversibly binding radioligands. J. Cereb. Blood Flow Metab. 27 (2007), 1533–1539.
47. Katafuchi, T., Kondo, T., Take, S., Yoshimura, M., Brain cytokines and the 5-HT system during poly I:C-induced fatigue. Ann. N. Y. Acad. Sci. 1088 (2006), 230–237.
48. Kelley, K.W., Bluthe, R., Dantzer, R., Zhou, J., Shen, W., Johnson, R.W., Broussard, S., Cytokine-induced sickness behaviour. Brain Behav. Immun. 17 (2003), S112–S118.
49. Kohler, O., Benros, M.E., Nordentoft, M., Farkouh, M.E., Iyengar, R.L., Mors, O., Krogh, J., Effect of anti-inflammatory treatment on depression, depressive symptoms, and adverse effects: a systematic review and meta-analysis of randomized clinical trials. JAMA Psychiatry 71 (2014), 1381–1391.
50. Kotyla, P., Jankiewicz-Ziobro, K., Owczarek, A., Kucharz, E.J., Etanercept increases tumor necrosis factor-alpha level but not sFas level in patients with rheumatoid arthritis. Isr. Med. Assoc. J. 17 (2015), 14–18.
51. Krishnadas, R., Etanercept for sleep in patients with alcohol use disorder–mechanisms need to be elucidated. Biol. Psychiatry, 67, 2010, e1 (author reply e3).
52. Krishnadas, R., Cavanagh, J., Depression: an inflammatory illness?. J. Neurol. Neurosurg. Psychiatry 83 (2012), 495–502.
53. Krishnan, R., Cella, D., Leonardi, C., Papp, K., Gottlieb, A.B., Dunn, M., Chiou, C.F., Patel, V., Jahreis, A., Effects of etanercept therapy on fatigue and symptoms of depression in subjects treated for moderate to severe plaque psoriasis for up to 96 weeks. Br. J. Dermatol. 157 (2007), 1275–1277.
54. Kurd, S.K., Troxel, A.B., Crits-Christoph, P., Gelfand, J.M., The risk of depression, anxiety, and suicidality in patients with psoriasis: a population-based cohort study. Arch. Dermatol. 146 (2010), 891–895.
55. Lampa, J., Westman, M., Kadetoff, D., Agreus, A.N., Le Maitre, E., Gillis-Haegerstrand, C., Andersson, M., Khademi, M., Corr, M., Christianson, C.A., Delaney, A., Yaksh, T.L., Kosek, E., Svensson, C.I., Peripheral inflammatory disease associated with centrally activated IL-1 system in humans and mice. Proc. Natl. Acad. Sci. U.S.A. 109 (2012), 12728–12733.
56. Langley, R.G., Feldman, S.R., Han, C., Schenkel, B., Szapary, P., Hsu, M.C., Ortonne, J.P., Gordon, K.B., Kimball, A.B., Ustekinumab significantly improves symptoms of anxiety, depression, and skin-related quality of life in patients with moderate-to-severe psoriasis: results from a randomized, double-blind, placebo-controlled phase III trial. J. Am. Acad. Dermatol. 63 (2010), 457–465.
57. 123I]beta-CIT: pharmacological characterization of brain uptake in nonhuman primates. Synapse 13 (1993), 295–309.
58. Liu, Y., Ho, R.C., Mak, A., Interleukin (IL)-6, tumour necrosis factor alpha (TNF-alpha) and soluble interleukin-2 receptors (sIL-2R) are elevated in patients with major depressive disorder: a meta-analysis and meta-regression. J. Affect. Disord. 139 (2012), 230–239.
59. Loftis, J.M., Patterson, A.L., Wilhelm, C.J., McNett, H., Morasco, B.J., Huckans, M., Morgan, T., Saperstein, S., Asghar, A., Hauser, P., Vulnerability to somatic symptoms of depression during interferon-alpha therapy for hepatitis C: a 16-week prospective study. J. Psychosom. Res. 74 (2013), 57–63.
60. Malynn, S., Campos-Torres, A., Moynagh, P., Haase, J., The pro-inflammatory cytokine TNF-alpha regulates the activity and expression of the serotonin transporter (SERT) in astrocytes. Neurochem. Res. 38 (2013), 694–704.
61. Massart, R., Mongeau, R., Lanfumey, L., Beyond the monoaminergic hypothesis: neuroplasticity and epigenetic changes in a transgenic mouse model of depression. Philos. Trans. R. Soc. Lond. B Biol. Sci. 367 (2012), 2485–2494.
62. Maximino, C., 2012. Serotonin in the Nervous System of Vertebrates. pp. 15–36.
63. Meyer, J.H., Applying neuroimaging ligands to study major depressive disorder. Semin. Nucl. Med. 38 (2008), 287–304.
64. Meyer, J.H., Neuroimaging markers of cellular function in major depressive disorder: implications for therapeutics, personalized medicine, and prevention. Clin. Pharmacol. Ther. 91 (2012), 201–214.
65. 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. 349 (1998), 317–324.
66. Mossner, R., Heils, A., Stober, G., Okladnova, O., Daniel, S., Lesh, K., Enhancement of serotonin transporter function by tumor necrosis factor alpha but not by interleukin-6. Neurochem. Int. 33 (1998), 251–254.
67. Myint, A.M., Schwarz, M.J., Steinbusch, H.W., Leonard, B.E., Neuropsychiatric disorders related to interferon and interleukins treatment. Metab. Brain Dis. 24 (2009), 55–68.
68. Nestle, F., Kaplan, D., Barker, J., Psoriasis. N. Engl. J. Med. 361 (2009), 496–509.
69. Palaniyappan, L., Liddle, P.F., Differential effects of surface area, gyrification and cortical thickness on voxel based morphometric deficits in schizophrenia. NeuroImage 60 (2012), 693–699.
70. Pfeilschifter, J., Koditz, R., Pfohl, M., Schatz, H., Changes in proinflammatory cytokine activity after menopause. Endocr. Rev. 23 (2002), 90–119.
71. Preacher, K.J., Hayes, A.F., Asymptotic and resampling strategies for assessing and comparing indirect effects in multiple mediator models. Behav. Res. Methods 40 (2008), 879–891.
72. Preskorn, S.H., The use of biomarkers in psychiatric research: how serotonin transporter occupancy explains the dose-response curves of SSRIs. J. Psychiatr. Pract. 18 (2012), 38–45.
73. Raison, C.L., Capuron, L., Miller, A.H., Cytokines sing the blues: inflammation and the pathogenesis of depression. Trends Immunol. 27 (2006), 24–31.
74. Raison, C.L., Rutherford, R.E., Woolwine, B.J., Shuo, C., Schettler, P., Drake, D.F., Haroon, E., Miller, A.H., A randomized controlled trial of the tumor necrosis factor antagonist infliximab for treatment-resistant depression: the role of baseline inflammatory biomarkers. JAMA Psychiatry 70 (2013), 31–41.
75. Ramamoorthy, S., Ramamoorthy, J., Prasad, P., Bhat, K., Mahesh, V., Leibach, F., Ganapathy, V., Regulation of the human serotonin transporter by interleukin 1B. Biochem. Biophys. Res. Commun. 216 (1995), 560–567.
76. Samuvel, D.J., A role for p38 mitogen-activated protein kinase in the regulation of the serotonin transporter: evidence for distinct cellular mechanisms involved in transporter surface expression. J. Neurosci. 25 (2005), 29–41.
77. Sassarini, J., Krishnadas, R., Cavanagh, J., Nicol, A., Pimlott, S.L., Ferrell, W., Lumsden, M.A., Venlafaxine alters microvascular perfusion, [(1)(2)(3)I]-beta-CIT binding and BDI scores in flushing postmenopausal women. Maturitas 77 (2014), 267–273.
78. Savitz, J.B., Drevets, W.C., Neuroreceptor imaging in depression. Neurobiol. Dis. 52 (2013), 49–65.
79. Schildkraut, J.J., The catecholamine hypothesis of affective disorders: a review of supporting evidence. Am. J. Psychiatry 122 (1965), 509–522.
80. Schmitt, J.M., Ford, D.E., Role of depression in quality of life for patients with psoriasis. Dermatology 215 (2007), 17–27.
81. Setiawan, E., Wilson, A.A., Mizrahi, R., Rusjan, P.M., Miler, L., Rajkowska, G., Suridjan, I., Kennedy, J.L., Rekkas, P.V., Houle, S., Meyer, J.H., Role of translocator protein density, a marker of neuroinflammation, in the brain during major depressive episodes. JAMA Psychiatry, 2015.
82. Skelly, D.T., Hennessy, E., Dansereau, M.A., Cunningham, C., A systematic analysis of the peripheral and CNS effects of systemic LPS, IL-1beta, [corrected] TNF-alpha and IL-6 challenges in C57BL/6 mice. PLoS ONE, 8, 2013, e69123.
83. Smith, R.S., The macrophage theory of depression. Med. Hypotheses 35 (1991), 298–306.
84. Stein, M., Miller, A.H., Trestman, R.L., Depression, the immune system, and health and illness. Findings in search of meaning. Arch. Gen. Psychiatry 48 (1991), 171–177.
85. Strike, P.C., Wardle, J., Steptoe, A., Mild acute inflammatory stimulation induces transient negative mood. J. Psychosom. Res. 57 (2004), 189–194.
86. Strober, B., Teller, C., Yamauchi, P., Miller, J.L., Hooper, M., Yang, Y.C., Dann, F., Effects of etanercept on C-reactive protein levels in psoriasis and psoriatic arthritis. Br. J. Dermatol. 159 (2008), 322–330.
87. Tan, J.K., Aphale, A., Malaviya, R., Sun, Y., Gottlieb, A.B., Mechanisms of action of etanercept in psoriasis. J. Investig. Dermatol. Symp. Proc. 12 (2007), 38–45.
88. Tsao, C.W., Lin, Y.S., Cheng, J.T., Lin, C.F., Wu, H.T., Wu, S.R., Tsai, W.H., Interferon-alpha-induced serotonin uptake in Jurkat T cells via mitogen-activated protein kinase and transcriptional regulation of the serotonin transporter. J. Psychopharmacol. 22 (2008), 753–760.
89. Tyring, S., Gottlieb, A., Papp, K., Gordon, K., Leonardi, C., Wang, A., Lalla, D., Woolley, M., Jahreis, A., Zitnik, R., Cella, D., Krishnan, R., Etanercept and clinical outcomes, fatigue, and depression in psoriasis: double-blind placebo-controlled randomised phase III trial. Lancet 367 (2006), 29–35.
90. Valkanova, V., Ebmeier, K.P., Allan, C.L., CRP, IL-6 and depression: a systematic review and meta-analysis of longitudinal studies. J. Affect. Disord. 150 (2013), 736–744.
91. Wallacelind, R., Bi-directional, chemically specified neural connections between the subfornical organ and the midbrain raphe system. Brain Res. 384 (1986), 250–261.
92. Yu, B., Becnel, J., Zerfaoui, M., Rohatgi, R., Boulares, A.H., Nichols, C.D., Serotonin 5-hydroxytryptamine (2A) receptor activation suppresses tumor necrosis factor-alpha-induced inflammation with extraordinary potency. J. Pharmacol. Exp. Ther. 327 (2008), 316–323.
93. Zhu, C.B., Blakely, R.D., Hewlett, W.A., The proinflammatory cytokines interleukin-1beta and tumor necrosis factor-alpha activate serotonin transporters. Neuropsychopharmacology 31 (2006), 2121–2131.
94. Zhu, C.B., Lindler, K.M., Owens, A.W., Daws, L.C., Blakely, R.D., Hewlett, W.A., Interleukin-1 receptor activation by systemic lipopolysaccharide induces behavioral despair linked to MAPK regulation of CNS serotonin transporters. Neuropsychopharmacology 35 (2010), 2510–2520.