Stress downregulates lipopolysaccharide-induced expression of proinflammatory cytokines in the spleen, pituitary, and brain of mice
Abstract
Mice injected with LPS (10 mu g/mouse, sc) or saline were submitted to a 15-min restraint stress and sacrificed 1 or 2 h later to assess the effect of stress on the induction of interleukin-1beta (IL-1beta) and other proinflammatory cytokines (IL-1alpha, IL-1ra, IL-6, and tumor necrosis factor-alpha) in the spleen, pituitary, hypothalamus, hippocampus, and striatum. LPS-induced cytokine gene expression, as determined by comparative RT-PCR, was lower in stressed than in nonstressed mice. LPS increased plasma and tissue levels of IL-1beta, as determined by ELISA, but this effect was less marked in stressed than in nonstressed mice. These results are discussed in relation to the modulatory effects of glucocorticoids on cytokine production.
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In the periphery, acute stress post-LPS decreases the production of IL-1β, TNF-α, and IL-6.
“By contrast, acute stress post-LPS decreases the production of these same cytokines (Goujon et al., 1995).”
From The Stressed CNS: When Glucocorticoids Aggravate Inflammation (2009) · cites this paper as Goujon et al., 1995
Acute stress or exogenous GCs can potentiate or conversely repress the same pro-inflammatory genes provided that they are respectively administered before or after LPS.
“Prior work established that acute stress or exogenous GCs can potentiate or conversely repress the same pro-inflammatory genes provided that they are respectively administered before or after LPS (140, 156).”
From The HPA – Immune Axis and the Immunomodulatory Actions of Glucocorticoids in the Brain (2014) · cites this paper as [156]
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Burgess, W., Gheusi, G., Yao, J. S., Johnson, R. W., Dantzer, R., & Kelley, K. W. (1998) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1998.274.6.r1829 · Cited by 43 · see citing works
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Layé, S., Goujon, E., Combe, C., VanHoy, R. W., Kelley, K. W., Parnet, P., & Dantzer, R. (1996) · Journal of Neuroimmunology · doi:10.1016/0165-5728(96)00066-5 · Cited by 40 · see citing works
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RIVIER, C. L. (1999) · Alcoholism Clinical and Experimental Research · doi:10.1111/j.1530-0277.1999.tb04169.x · Cited by 37 · see citing works
Pagliarone, A. C., Orsatti, C. L., Búfalo, M. C., Missima, F., Bachiega, T. F., Araújo, J. P., & Sforcin, J. M. (2009) · International Immunopharmacology · doi:10.1016/j.intimp.2009.08.005 · Cited by 38 · see citing works
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Ashcraft, K. A., Hunzeker, J., & Bonneau, R. H. (2008) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2008.04.010 · Cited by 33 · see citing works
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Quabius, E. S., Krupp, G., & Secombes, C. J. (2005) · Environmental Toxicology and Chemistry · doi:10.1897/05-110r.1 · Cited by 32 · see citing works
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Barbier, L., Diserbo, M., Lamproglou, I., Amourette, C., Peinnequin, A., & Fauquette, W. (2008) · Behavioural Brain Research · doi:10.1016/j.bbr.2008.08.032 · Cited by 27 · see citing works
Myles, E. M., O’Leary, M. E., Smith, R., MacPherson, C. W., Oprea, A., Melanson, E. H., Tompkins, T. A., & Perrot, T. S. (2020) · Microorganisms · doi:10.3390/microorganisms8101527 · Cited by 27 · see citing works
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BackgroundBiesmans, S., Acton, P. D., Cotto, C., Langlois, X., Donck, L. V., Bouwknecht, J. A., Aelvoet, S., Hellings, N., Meert, T. F., & Nuydens, R. (2015) · Glia · doi:10.1002/glia.22804 · Cited by 25 · see citing works
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ResultStressor-induced modulation of immune function: a review of acute, chronic effects in animals
Kusnecov, A. W., & Rossi‐George, A. (2002) · Acta Neuropsychiatrica · doi:10.1034/j.1601-5215.2002.140603.x · Cited by 24 · see citing works
Franklin, A. E., Engeland, C. G., Kavaliers, M., et al. (2007) · Behavioural Brain Research · doi:10.1016/j.bbr.2007.03.021 · Cited by 23 · see citing works
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Taylor, A. N., Tio, D. L., & Yirmiya, R. (1999) · Journal of Neuroimmunology · doi:10.1016/s0165-5728(99)00102-2 · Cited by 21 · see citing works
Gibb, J., Al‐Yawer, F., & Anisman, H. (2012) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2012.11.004 · Cited by 22 · see citing works
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BackgroundActivation of the Hypothalamic- Pituitary-Adrenal Axis in IL-1β-Converting Enzyme-Deficient Mice
Liège, S., Moze, E., Kelley, K. W., Parnet, P., & Neveu, P. J. (2000) · NeuroImmunoModulation · doi:10.1159/000026438 · Cited by 20 · see citing works
Self-citationZhu, Q., Emanuele, M. A., LaPaglia, N., Kovacs, E. J., & Emanuele, N. (2007) · Endocrine · doi:10.1007/s12020-007-9010-5 · Cited by 19 · see citing works
“Hypothalamus is one of the sites of TNF-a synthesis [16–19].”
BackgroundCytokines, Sickness Behavior, and Depression
Dantzer, R., Bluthé, R.-M., Castanon, N., Kelley, K. W., Konsman, J. P., Layé, S., Lestage, J., & Parnet, P. (2007) · Elsevier eBooks · doi:10.1016/b978-012088576-3/50019-8 · Cited by 32 · see citing works
Self-citationIncreased Sensitivity of Prediabetic Nonobese Diabetic Mouse to the Behavioral Effects of IL-1
Bluthé, R.-M., Jafarian-Tehrani, M., Michaud, B., Haour, F., Dantzer, R., & Homo‐Delarche, F. (1999) · Brain Behavior and Immunity · doi:10.1006/brbi.1998.0542 · Cited by 18 · see citing works
Self-citationEmanuele, N., LaPaglia, N., Kovacs, E. J., & Emanuele, M. A. (2005) · Endocrine Research · doi:10.1080/07435800500228930 · Cited by 17 · see citing works
Intrapituitary cytokines in Cushing’s disease: do they play a role?
Paoletta, A., Arnaldi, G., Papa, R., Boscaro, M., & Tirabassi, G. (2010) · Pituitary · doi:10.1007/s11102-010-0285-9 · Cited by 15 · see citing works
“In particular, cytokines seem to play an important role in regulating the hypothalamic–pituitary–adrenal axis function [3] and in turn can be influenced by it [4–8].”
BackgroundChapter 11 Immunological and neuroendocrine modulation of fever in stress
Roth, J. (1998) · Progress in brain research · doi:10.1016/s0079-6123(08)62036-1 · Cited by 15 · see citing works
The Impact of Social and Physical Peer Victimization on Systemic Inflammation in Adolescents
Araña, A. A., Boyd, E. Q., Guarneri-White, M. E., Iyer‐Eimerbrink, P. A., Dougall, A. L., & Jensen‐Campbell, L. A. (2018) · Merrill-palmer Quarterly · doi:10.13110/merrpalmquar1982.64.1.0012 · Cited by 15 · see citing works
“These results are particularly difficult to reconcile, as this is the first study to date to evaluate the unique effects of physical peer victimization on inflammatory biomarkers and one of very few to report an inverse relationship between stress and inflammation (see Goujon et al., 1995).”
ResultScott, K. A., Phan, T., Boukelmoune, N., Heijnen, C. J., & Dantzer, R. (2022) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2022.10.017 · Cited by 13 · see citing works
Self-citationGavrilov, Y. V., Перекрест, С. В., & Novikova, N. S. (2007) · Neuroscience and Behavioral Physiology · doi:10.1007/s11055-008-0012-4 · Cited by 13 · see citing works
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BackgroundChromatin organization as an indicator of glucocorticoid induced natural killer cell dysfunction
Misale, M. S., Janusek, L. W., Tell, D., & Mathews, H. L. (2017) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2017.09.004 · Cited by 11 · see citing works
Systemic administration of betamethasone delays endotoxin-induced preterm labor in the murine model
Schwartz, W. J., Christensen, H. D., Carey, J. C., Rayburn, W. F., & Gonzalez, C. L. (2003) · American Journal of Obstetrics and Gynecology · doi:10.1067/mob.2003.72 · Cited by 11 · see citing works
Mahanti, S., Majhi, A., Chongdar, S., Kundu, K., Dutta, K., Basu, A., & Bishayi, B. (2012) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2012.11.001 · Cited by 10 · see citing works
“It is well known that bacterial endotoxin is a potent stimulator for the synthesis and release of proinflammatory cytokines such as IL-6, TNF-a, IFN-c, but acute stress has been shown to downregulate these LPS-induced responses (Goujon et al., 1995) IL-6 is essential for activation of HPA axis during immunological cha…”
Floreste, F. R., Titon, B., Titon, S. C. M., Muxel, S. M., de Figueiredo, A. C., Gomes, F. R., & Assis, V. R. (2022) · Comparative Biochemistry and Physiology Part B Biochemistry and Molecular Biology · doi:10.1016/j.cbpb.2022.110784 · Cited by 9 · see citing works
Aubrecht, T. G., Weil, Z. M., Ariza, M. E., Williams, M., Reader, B. F., Glaser, R., Sheridan, J. F., & Nelson, R. J. (2014) · Physiology & Behavior · doi:10.1016/j.physbeh.2014.07.001 · Cited by 9 · see citing works
“Therefore, short periods of restraint stress, which increase glucocorticoids, can decrease proinflammatory cytokine expression even in response to LPS injections [18].”
BackgroundGavrilov, Y. V., Перекрест, С. В., Novikova, N. S., & Korneva, E. A. (2008) · Neuroscience and Behavioral Physiology · doi:10.1007/s11055-008-0028-9 · Cited by 9 · see citing works
“A number of studies [ 16 , 19] have demonstrated decreases in interleukin-1 and tumor necrosis factor levels in the spleens of rats after administration of lipopolysaccharide on the background of electrical pain stimulation.”
ResultImmunophysiology: The Interaction of Hormones, Lymphohemopoietic Cytokines, and the Neuroimmune Axis
Arkins, S., Johnson, R. W., Minshall, C. T., Dantzer, R., & Kelley, K. W. (2001) · Comprehensive physiology · doi:10.1002/cphy.cp070421 · Cited by 9 · see citing works
Self-citationMehrzad, J., Shajari, M., Saleh-moghaddam, M., & Mohammad, S. N. (2015) · International Immunopharmacology · doi:10.1016/j.intimp.2015.05.041 · Cited by 7 · see citing works
Teramura, Y., Terao, A., Okada, Y., Tomida, J., Okamatsu‐Ogura, Y., & Kimura, K. (2014) · PubMed · doi:10.14943/jjvr.62.3.117 · Cited by 6 · see citing works
“LPS-induced cytokine production was reduced in the plasma and brain by immobilization [9].”
BackgroundEmanuele, N., LaPaglia, N., Kovacs, E. J., Gamelli, R. L., & Emanuele, M. A. (2008) · Journal of Burn Care & Research · doi:10.1097/bcr.0b013e3181711273 · Cited by 4 · see citing works
Immunomodulatory T cell death associated gene-8 (TDAG8) receptor in depression-associated behaviors
McMurray, K. M. J., Vollmer, L. L., Ahlbrand, R. A., Thomas, J. D., Winter, A. S., Lewkowich, I. P., & Sah, R. (2019) · Physiology & Behavior · doi:10.1016/j.physbeh.2019.112598 · Cited by 3 · see citing works
“Given contributions of the spleen in immune dysfunction associated with stress and depression-like behaviors, we next assessed cytokine levels within this tissue[46,47].”
BackgroundTillinger, A., Padová, A., Mravec, B., & Tomova, A. (2019) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2019.577030 · Cited by 3 · see citing works
Gut microbiota and immune response under chronic social stress in an LPS-induced inflammatory model
Petakh, P., Stravskyy, Y. S., Halabitska, I., Pavliuk, A., & Kamyshnyi, O. (2025) · Stress · doi:10.1080/10253890.2025.2595777 · Cited by 2 · see citing works
“Experimental studies in rodents have also demonstrated that prior exposure to acute or chronic stress can “prime” the innate immune system, resulting in exaggerated cytokine release upon subsequent inflammatory challenge (Frank et al., 2016; Goujon et al., 1995).”
Глюкокортикоиды в нейровоспалении гиппокампа: доктор Джекилл и мистер Хайд
Bolshakov, A. P., Третьякова, Л. В., Квичанский, А. А., & Гуляева, Н. В. (2021) · Biochemistry (Moscow) · doi:10.31857/s0320972521020044 · Cited by 2 · see citing works
Mechanisms of action of cytokines on the central nervous system. Interaction with glucocorticoids
Dantzer, R., Layé, S., Goujan, E., et al. (1997) · Springer eBooks · doi:10.1007/978-1-4471-0931-0_1 · Cited by 2 · see citing works
Self-citationDepression and immunity: biological and behavioural mechanisms
Irwin, M. R. (2006) · Cambridge University Press eBooks · doi:10.1017/cbo9780511544293.015 · Cited by 2 · see citing works
McConn, B. R., Kpodo, K. R., Rivier, J., Behan, D. P., Richert, B. T., Radcliffe, J. S., Lay, D. C., Jr., & Johnson, J. S. (2023) · Frontiers in Physiology · doi:10.3389/fphys.2023.1266409 · Cited by 1 · see citing works
Reciprocal Brain-Body Neuro-Endocrine-Immune Interactions: Role in Maintaining Pregnancy
Parker, V. J., Arck, P., & Douglas, A. J. (2011) · Advances in Neuroimmune Biology · doi:10.3233/nib-2011-020 · Cited by 1 · see citing works
Glucocorticoids: Immunity and Inflammation
Ronchetti, S., & Riccardi, C. (2018) · Springer eBooks · doi:10.1007/978-3-319-77658-3_12 · Cited by 1 · see citing works
O’Loughlin, A. (2011) · Maynooth University ePrints and eTheses Archive (Maynooth University) · Cited by 1 · see citing works
Brain Interleukin-1β Expression and Action in the Absence of Neuropathology
Chaskiel, L., & Konsman, J. P. (2008) · Neuroimmune biology · doi:10.1016/s1567-7443(07)10004-1
Mimouni, J., Farine, J. C., Melhaoui, A., et al. (1997) · International Journal of Immunopharmacology · doi:10.1016/s0192-0561(97)00051-9
Martin, S. A. (2013) · Illinois Digital Environment for Access to Learning and Scholarship (University of Illinois at Urbana-Champaign)
- Authors
- Goujon, E., Parnet, P., Laye, S., Combe, C., Kelley, K. W., & Dantzer, R.
- Affiliations
- Inserm (FR)
- Venue
- Brain Behavior and Immunity
- Publisher
- Elsevier BV
- Published
- 1995-12
- Volume
- 9
- Issue
- 4
- Pages
- 292-303
- ISSN
- 0889-1591 (ISSN-L)
- OpenAlex
- W2032191599
- Cited by
- 106
- References
- 0
- Citations by year
- 2025: 1 · 2023: 1 · 2022: 3 · 2021: 2 · 2020: 1 · 2019: 2 · 2018: 3 · 2017: 4 · 2015: 6 · 2014: 6 · 2013: 4 · 2012: 4
- FWCI
- 1.78
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Brain Behavior and Immunity (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Funders
- National Institutes of Health (5r01dk049311-05)
- National Institute of Mental Health (1RO1 MH51569-01A2, R01MH051569)
- National Institute of Diabetes and Digestive and Kidney Diseases (1RO1 DK 49311)
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Keywords
- restraint stress, lipopolysaccharide, inflammatory cytokines, IL-1β, interleukin-1 alpha, interleukin-1 receptor antagonist, interleukin-6, TNF-α, glucocorticoids, hypothalamic-pituitary-adrenal axis, spleen, pituitary gland, hippocampus, striatum, cytokine gene expression, neuroimmune interactions
- MeSH terms
- Animals, Brain, Corpus Striatum, Corticosterone, Gene Expression Regulation, Hippocampus, Hypothalamus, Interleukin-1, Lipopolysaccharides, Male, Mice, Inbred ICR, Pituitary Gland, Restraint, Physical, RNA, Messenger, Sialoglycoproteins, Spleen, Stress, Physiological, Tumor Necrosis Factor-alpha, Neuroimmunomodulation, Interleukin-6, Mice, Interleukin 1 Receptor Antagonist Protein
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