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Reciprocal regulation of the neural and innate immune systems
Open accessAbstract
Innate immune responses are regulated by microorganisms and cell death, as well as by a third class of stress signal from the nervous and endocrine systems. The innate immune system also feeds back, through the production of cytokines, to regulate the function of the central nervous system (CNS), and this has effects on behaviour. These signals provide an extrinsic regulatory circuit that links physiological, social and environmental conditions, as perceived by the CNS, with transcriptional 'decision-making' in leukocytes. CNS-mediated regulation of innate immune responses optimizes total organism fitness and provides new opportunities for therapeutic control of chronic infectious, inflammatory and neuropsychiatric diseases.
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“Two physiological pathways are responsible for converting social-environmental adversity into broad proinflammatory transcriptional programs such as the CTRA.”
From From stress to inflammation and major depressive disorder: A social signal transduction theory of depression. (2014) · cites this paper as Irwin & Cole, 2011
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Although these regions do not directly regulate inflammatory activity, they have anatomical connections to lower level brain regions, including the hypothalamus and brainstem autonomic control nuclei, which influence systemic inflammation by modulating the activity of the HPA axis and SNS”
From From stress to inflammation and major depressive disorder: A social signal transduction theory of depression. (2014) · cites this paper as Irwin & Cole, 2011
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“This hypothesis grows out of mounting evidence that severe childhood stressors promote the formation of a neural-immune pipeline (15), wherein inflammatory cytokine signaling between the brain and the periphery is markedly amplified (16).”
From Clustering of depression and inflammation in adolescents previously exposed to childhood adversity (2012) · cites this paper as [16]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Once released, norepinephrine modulates immune response gene transcription via stimulation of β -adrenergic receptors”
From From stress to inflammation and major depressive disorder: A social signal transduction theory of depression. (2014) · cites this paper as Irwin & Cole, 2011
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In the citing paper
“a biologically plausible pathway exists by which stressors occurring in the social environment may influence inflammatory activity”
From From stress to inflammation and major depressive disorder: A social signal transduction theory of depression. (2014) · cites this paper as Irwin & Cole, 2011
The cited source says what the claim attributes to it.
In the citing paper
“the brain can modulate inflammatory activity throughout the body via the processes described earlier -namely, SNS-related β -adrenergic signaling and HPA axis-related cortisol production”
From From stress to inflammation and major depressive disorder: A social signal transduction theory of depression. (2014) · cites this paper as Irwin & Cole, 2011
In the citing paper
“When threat is perceived, the SNS releases noradrenaline, which promotes mobilization of stem cells from the bone marrow and activates immune gene transcription within white blood cells, organs, and tissues (Irwin and Cole, 2011).”
From Developmental psychoneuroendocrine and psychoneuroimmune pathways from childhood adversity to disease (2017) · cites this paper as Irwin and Cole, 2011
In the citing paper
“Parallel studies on the transcriptional correlates of social disparities in health subsequently suggested that both physical and psychological processes contribute to the net effect of a given social environment, with each mechanism activating some distinct gene modules as well as a conserved generalized response to adverse life circumstances (Figure 1) [3], [5], [12].”
From Human Social Genomics (2014) · cites this paper as [5]
In the citing paper
“Genes up-regulated in socially isolated individuals included a set of transcripts that play a central role in inflammation (e.g., IL1B, IL8, PTGS2), whereas down-regulated transcripts were involved in Type I interferon innate antiviral responses (e.g., ISG, IFI, MX, and OAS family genes) and in antibody production (e.g., IGL, IGH, IGJ, and IGK) [5], [14], [15].”
From Human Social Genomics (2014) · cites this paper as [5]
In the citing paper
“Across these diverse forms of adversity, a common pattern of conserved transcriptional response to adversity (CTRA) has emerged, including increased expression of proinflammatory genes and decreased expression of genes involved in Type I interferon innate antiviral responses and IgG antibody synthesis [3], [5], [28].”
From Human Social Genomics (2014) · cites this paper as [5]
In the citing paper
“In both, chronic threat and SNS signaling activate tissue-specific transcriptional defense programs that enhance organismic mobility and prime wound healing and antimicrobial responses to tissue injury [3], [5], [36].”
From Human Social Genomics (2014) · cites this paper as [5]
In the citing paper
“substantial evidence demonstrates a reciprocal relationship between the CNS and innate immunity (Dantzer et al, 2008(Dantzer et al, , 2012;;Irwin and Cole, 2011).”
From Sleep health: Reciprocal regulation of sleep and innate immunity (2017) · cites this paper as Irwin and Cole, 2011
In the citing paper
“the SNS allows the CNS to 'steer' innate immune responses between proinflammatory and antiviral phenotypes”
From Sleep health: Reciprocal regulation of sleep and innate immunity (2017) · cites this paper as Irwin and Cole, 2011
In the citing paper
“with evidence that sleep disturbance leads to a similar response”
From Sleep health: Reciprocal regulation of sleep and innate immunity (2017) · cites this paper as Irwin and Cole, 2011
In the citing paper
“norepinephrine regulates immune response gene transcription and proinflammatory cytokine production via stimulation of β-adrenergic receptors”
From Sleep health: Reciprocal regulation of sleep and innate immunity (2017) · cites this paper as Irwin and Cole, 2011
In the citing paper
“the conserved transcriptional response to adversity (CTRA), and is characterized by increased proinflammatory and reduced antiviral skewing of the basal gene expression profile”
From Sleep health: Reciprocal regulation of sleep and innate immunity (2017) · cites this paper as Irwin and Cole, 2011
In the citing paper
“which increases an individual's risk for both viral infection and inflammation-related disease”
From Sleep health: Reciprocal regulation of sleep and innate immunity (2017) · cites this paper as Irwin and Cole, 2011
In the citing paper
“the host defense program is activated by non-physical social, symbolic, anticipated, or imagined threats”
From Sleep health: Reciprocal regulation of sleep and innate immunity (2017) · cites this paper as Irwin and Cole, 2011
In the citing paper
“The inhibitory effects of glucocorticoid activation on immune response gene transcription is mediated by at least three mechanisms.”
From Sleep health: Reciprocal regulation of sleep and innate immunity (2017) · cites this paper as Irwin and Cole, 2011
In the citing paper
“Furthermore, hypocortisolimia diminishes negative feedback control of inflammatory cytokines, resulting in the persistent pro-inflammatory profile that is observed in adults with ELAb.(76,77)”
In the citing paper
“In what neuroimmunologist Stephen Cole refers to as the Conserved Transcriptional Response to Adversity (CTRA), increased chronic social adversity is associated with white blood cells amplifying transcription and expression of proinflammatory cytokines (Irwin & Cole, 2011).”
From On race, human variation, and who gets and dies of sepsis (2022) · cites this paper as Irwin & Cole, 2011
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Citations
Cites
Molecular Mechanisms of Depression: Perspectives on New Treatment Strategies
Lang, U. E., & Borgwardt, S. (2013) · Cellular Physiology and Biochemistry · doi:10.1159/000350094 · Cited by 8,526
From inflammation to sickness and depression: when the immune system subjugates the brain
Dantzer, R., O'Connor, J. C., Freund, G. G., Johnson, R. W., & Kelley, K. W. (2008) · Nature Reviews Neuroscience · doi:10.1038/nrn2297 · Cited by 7,395
Physiology and neurobiology of stress and adaptation: central role of the brain
McEwen, B. S. (2007) · Physiological Reviews · doi:10.1152/physrev.00041.2006 · Cited by 5,429 · cited 1×
“Such threats can be microbial, physiological (such as trauma and sleep loss) or social–ecological (such as predation, conspecific violence and interpersonal loss) in natur”
BackgroundInflammation and Its Discontents: The Role of Cytokines in the Pathophysiology of Major Depression
Miller, A. H., Maletic, V., & Raison, C. L. (2009) · Biological Psychiatry · doi:10.1016/j.biopsych.2008.11.029 · Cited by 3,848
Psychological Stress and Disease
Cohen, S., Janicki-Deverts, D., & Miller, G. E. (2007) · JAMA · doi:10.1001/jama.298.14.1685 · Cited by 3,168 · cited 1×
“We map the molecular signalling pathways involved in this reciprocal regulation, discuss their implications for social influences on diseas”
BackgroundAntiinflammatory Action of Glucocorticoids — New Mechanisms for Old Drugs
Rhen, T., & Cidlowski, J. A. (2005) · New England Journal of Medicine · doi:10.1056/nejmra050541 · Cited by 3,149 · cited 1×
“This effect is mediated by three mechanisms, namely: suppressive binding of the glucocorticoid receptor to gene promoter sequences; glucocorticoid receptor-mediated transcriptional induction of anti-inflammatory genes (such as NFKBIA , which encodes IκBα); and non-genomic antagonism of pro-inflammatory transcription f…”
BackgroundBiological basis of the behavior of sick animals
Hart, B. L. (1988) · Neuroscience & Biobehavioral Reviews · doi:10.1016/s0149-7634(88)80004-6 · Cited by 2,223 · cited 1×
“Moreover, these cytokines activate physiological and behavioural responses, such as fever and social withdrawal, which function together with leukocyte activation dynamics to limit the spread of infectious disease both within and between individual”
BackgroundStress-induced immune dysfunction: implications for health
Glaser, R., & Kiecolt-Glaser, J. K. (2005) · Nature Reviews Immunology · doi:10.1038/nri1571 · Cited by 2,190 · cited 1×
“A growing body of research shows that a third class of stimulus, in the form of neural and endocrine signals that result from macroenvironmental sensing, also plays a significant role in modulating immune response”
Immunoregulatory Feedback Between Interleukin-1 and Glucocorticoid Hormones
Besedovsky, H., del Rey, A., Sorkin, E., & Dinarello, C. A. (1986) · Science · doi:10.1126/science.3014662 · Cited by 1,519 · cited 1×
“The earliest identified CNS-mediated immunoregulatory function involved the brain's ability to suppress the transcription of both pro-inflammatory and antiviral gene programmes by stimulating glucocorticoid release from the HPA axi”
BackgroundInterleukin-1 stimulates the secretion of hypothalamic corticotropin-releasing factor
Sapolsky, R., Rivier, C., Yamamoto, G., Plotsky, P., & Vale, W. (1987) · Science · doi:10.1126/science.2821621 · Cited by 1,504 · cited 1×
“The earliest identified CNS-mediated immunoregulatory function involved the brain's ability to suppress the transcription of both pro-inflammatory and antiviral gene programmes by stimulating glucocorticoid release from the HPA axi”
BackgroundChronic stress and age-related increases in the proinflammatory cytokine IL-6.
Kiecolt-Glaser, J. K., Preacher, K. J., MacCallum, R. C., Atkinson, C., Malarkey, W. B., & Glaser, R. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1531903100 · Cited by 1,267
Effect of sleep loss on C-reactive protein, an inflammatory marker of cardiovascular risk
Meier-Ewert, H. K., Ridker, P. M., Rifai, N., Regan, M. M., Price, N. J., Dinges, D. F., & Mullington, J. M. (2004) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2003.07.050 · Cited by 1,195
Corticotropin-releasing factor-producing neurons in the rat activated by interleukin-1
Berkenbosch, F., van Oers, J., del Rey, A., Tilders, F., & Besedovsky, H. (1987) · Science · doi:10.1126/science.2443979 · Cited by 1,151
Tyring, S., Gottlieb, A., Papp, K., Gordon, K., Leonardi, C., Wang, A., Lalla, D., Woolley, M., Jahreis, A., Zitnik, R., et al. (2006) · The Lancet · doi:10.1016/s0140-6736(05)67763-x · Cited by 1,069 · cited 1×
“Conversely, pharmacological antagonism of TNF has been shown to reduce depressive symptom”
BackgroundThe sympathetic nervous system induces a metastatic switch in primary breast cancer
Sloan, E. K., Priceman, S. J., Cox, B. F., Yu, S., Pimentel, M. A., Tangkanangnukul, V., Arevalo, J. M. G., Morizono, K., Karanikolas, B. D. W., Wu, L., et al. (2010) · Cancer Research · doi:10.1158/0008-5472.can-10-0522 · Cited by 930
Self-citationA mechanism converting psychosocial stress into mononuclear cell activation
Bierhaus, A., Wolf, J., Andrassy, M., Rohleder, N., Humpert, P. M., Petrov, D., Ferstl, R., von Eynatten, M., Wendt, T., Rudofsky, G., et al. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0438019100 · Cited by 927 · cited 1×
“, activate NF-κB in peripheral blood mononuclear cell”
BackgroundAutonomic innervation and regulation of the immune system (1987–2007)
Nance, D. M., & Sanders, V. M. (2007) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2007.03.008 · Cited by 855 · cited 1×
“The neural fibres of the SNS distribute the neurotransmitter noradrenaline into tissue microenvironments in which immune response gene transcription occurs, including all primary and secondary lymphoid organs, the vasculature and perivascular tissues, and most visceral organs and musculoskeletal structure”
Sleep Deprivation and Activation of Morning Levels of Cellular and Genomic Markers of Inflammation
Irwin, M. R. (2006) · Archives of Internal Medicine · doi:10.1001/archinte.166.16.1756 · Cited by 850 · cited 1×
“Wake–sleep cycles have emerged as prominent regulators of inflammatory biology, with experimental sleep restriction studies showing upregulated leukocyte expression of pro-inflammatory cytokine genes and increased NF-κB activit”
BackgroundSelf-citationMiller, G. E., Chen, E., Fok, A. K., Walker, H., Lim, A., Nicholls, E. F., Cole, S., & Kobor, M. S. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0902971106 · Cited by 822
Self-citationPace, T. W. W., Mletzko, T. C., Alagbe, O., Musselman, D. L., Nemeroff, C. B., Miller, A. H., & Heim, C. M. (2006) · American Journal of Psychiatry · doi:10.1176/ajp.2006.163.9.1630 · Cited by 810 · cited 1×
“Laboratory animal and human studies have confirmed that experimental induction of acute psychological stress can increase circulating levels of IL-6 and IL-1”
BackgroundCapuron, L. (2002) · Neuropsychopharmacology · doi:10.1016/s0893-133x(01)00407-9 · Cited by 797
Harrison, N. A., Brydon, L., Walker, C., Gray, M. A., Steptoe, A., & Critchley, H. D. (2009) · Biological Psychiatry · doi:10.1016/j.biopsych.2009.03.015 · Cited by 756 · cited 1×
“The findings have shown altered connectivity between the subgenual anterior cingulate cortex, amygdala and medial prefrontal corte”
BackgroundPace, T. W. W., Negi, L. T., Adame, D. D., Cole, S. P., Sivilli, T. I., Brown, T. D., Issa, M. J., & Raison, C. L. (2009) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2008.08.011 · Cited by 748
Self-citationSocial regulation of gene expression in human leukocytes
Cole, S. W., Hawkley, L. C., Arevalo, J. M., Sung, C. Y., Rose, R. M., & Cacioppo, J. T. (2007) · Genome Biology · doi:10.1186/gb-2007-8-9-r189 · Cited by 745 · cited 1×
“Collectively, these studies of neuro–immune regulation have provided new insights into the mechanistic relationships between the cellular and microbial microenvironment in which immune responses have traditionally been analysed and the broader macroenvironment of the host body and its surrounding social and physical e…”
BackgroundSelf-citationHow (and why) the immune system makes us sleep
Imeri, L., & Opp, M. R. (2009) · Nature Reviews Neuroscience · doi:10.1038/nrn2576 · Cited by 710 · cited 1×
“Pro-inflammatory cytokines and type I IFNs also have a role in the homeostatic regulation of slee”
BackgroundEricsson, A. B., Kovacs, K., & Sawchenko, P. E. (1994) · Journal of Neuroscience · doi:10.1523/jneurosci.14-02-00897.1994 · Cited by 679
Wohleb, E. S., Hanke, M. L., Corona, A. W., Powell, N. D., Stiner, L. M., Bailey, M. T., Nelson, R. J., Godbout, J. P., & Sheridan, J. F. (2011) · The Journal of Neuroscience · doi:10.1523/jneurosci.0450-11.2011 · Cited by 638
Neuroendocrine-Immune Mechanisms of Behavioral Comorbidities in Patients With Cancer
Miller, A. H., Ancoli‐Israel, S., Bower, J. E., Capuron, L., & Irwin, M. R. (2008) · Journal of Clinical Oncology · doi:10.1200/jco.2007.10.7805 · Cited by 625 · cited 1×
“, and documented increased rates of MDD in clinical conditions involving high levels of inflammation (for example, in patients with cancer”
BackgroundSelf-citationPace, T. W. W., Hu, F., & Miller, A. H. (2007) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2006.08.009 · Cited by 621
Inflammation-Induced Anhedonia: Endotoxin Reduces Ventral Striatum Responses to Reward
Eisenberger, N. I., Berkman, E. T., Inagaki, T. K., Rameson, L. T., Mashal, N. M., & Irwin, M. R. (2010) · Biological Psychiatry · doi:10.1016/j.biopsych.2010.06.010 · Cited by 596
Self-citationHealthy Older Adults’ Sleep Predicts All-Cause Mortality at 4 to 19 Years of Follow-Up
Dew, M. A., Hoch, C. C., Buysse, D. J., Monk, T. H., Begley, A. E., Houck, P. R., Hall, M., Kupfer, D. J., & Reynolds, C. F. (2003) · Psychosomatic Medicine · doi:10.1097/01.psy.0000039756.23250.7c · Cited by 587 · cited 1×
“, as well as the epidemiological links between abnormally high levels of REM sleep and mortalit”
BackgroundGimeno, D., Kivimäki, M., Brunner, E. J., Elovainio, M., De Vogli, R., Steptoe, A., Kumari, M., Lowe, G. D. O., Rumley, A., Marmot, M. G., et al. (2009) · Psychological Medicine · doi:10.1017/s0033291708003723 · Cited by 561 · cited 1×
“Consistent with this hypothesis, epidemiological studies have linked IL-6 and TNF levels with the risk of developing MD”
ResultMiller, G. E., Chen, E., Sze, J., Marin, T., Arevalo, J. M. G., Doll, R., Ma, R., & Cole, S. W. (2008) · Biological Psychiatry · doi:10.1016/j.biopsych.2008.03.017 · Cited by 552
Self-citationFriendly and dangerous signals: is the tissue in control?
Matzinger, P. (2006) · Nature Immunology · doi:10.1038/ni0107-11 · Cited by 533 · cited 1×
“Transcriptional activation in innate immune cells is triggered by two types of signal from the body's internal environment: pathogen-associated molecular patterns (PAMPs) and 'danger signals' derived from host cell stress or deat”
BackgroundUnbiased Reconstruction of a Mammalian Transcriptional Network Mediating Pathogen Responses
Amit, I., Garber, M., Chevrier, N., Leite, A. P., Donner, Y., Eisenhaure, T., Guttman, M., Grenier, J. K., Li, W., Zuk, O., et al. (2009) · Science · doi:10.1126/science.1179050 · Cited by 488 · cited 1×
“Immune response gene regulation Functional genomics studies have identified two broad gene expression programmes that can be induced in myeloid lineage cells by different types of microbial stimulu”
BackgroundThe Yin and Yang of type I interferon activity in bacterial infection
Decker, T., Müller, M. M., & Stockinger, S. (2005) · Nature reviews. Immunology · doi:10.1038/nri1684 · Cited by 486 · cited 1×
“These two gene expression programmes mediate fundamentally different effector response”
BackgroundSleep Loss Activates Cellular Inflammatory Signaling
Irwin, M. R., Wang, M., Ribeiro, D., Cho, H. J., Olmstead, R., Breen, E. C., Martinez-Maza, O., & Cole, S. (2008) · Biological Psychiatry · doi:10.1016/j.biopsych.2008.05.004 · Cited by 467 · cited 1×
“Wake–sleep cycles have emerged as prominent regulators of inflammatory biology, with experimental sleep restriction studies showing upregulated leukocyte expression of pro-inflammatory cytokine genes and increased NF-κB activit”
BackgroundSelf-citationBeta2-agonists prevent Th1 development by selective inhibition of interleukin 12.
Panina‐Bordignon, P., Mazzeo, D., Lucia, P. D., D’Ambrosio, D., Lang, R., Fabbri, L. M., Self, C., & Sinigaglia, F. (1997) · Journal of Clinical Investigation · doi:10.1172/jci119674 · Cited by 461
Zautra, A. J., Davis, M. C., Reich, J. W., Nicassario, P., Tennen, H., Finan, P., Kratz, A., Parrish, B., & Irwin, M. R. (2008) · Journal of Consulting and Clinical Psychology · doi:10.1037/0022-006x.76.3.408 · Cited by 430 · cited 1×
“Randomized controlled trials have documented reductions in pro-inflammatory cytokine activity following several types of behavioural intervention ( Box 3 ), including cognitive behavioural therap”
BackgroundSelf-citationFinch, C. E. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0909606106 · Cited by 417
Inflammatory Biomarkers for Persistent Fatigue in Breast Cancer Survivors
Collado-Hidalgo, A., Bower, J. E., Ganz, P. A., Cole, S. W., & Irwin, M. R. (2006) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-05-2398 · Cited by 395
Self-citationLee, H. J., Takemoto, N., Kurata, H., Kamogawa, Y., Miyatake, S., O'Garra, A., & Arai, N. (2000) · The Journal of Experimental Medicine · doi:10.1084/jem.192.1.105 · Cited by 393 · cited 1×
“β-adrenergic signalling was initially found to modulate adaptive immune responses by stimulating the transcription of T helper 2 (T H 2)-type cytokine genes (such as IL4 and IL5 ) and suppressing the expression of T H 1-type genes (such as IFNG and IL12B”
BackgroundSchubert, C., Hong, S., Natarajan, L., Mills, P. J., & Dimsdale, J. E. (2006) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2006.11.004 · Cited by 371
Vgontzas, A. N., Zoumakis, E., Lin, H. ‐., Bixler, E. O., Trakada, G., & Chrousos, G. P. (2004) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2003-031929 · Cited by 345 · cited 1×
“Elevated daytime levels of TNF have also been linked with sleepiness, fatigue and altered sleep architecture, and pharmacological antagonism of TNF can reduce these effect”
BackgroundFatigue in multiple sclerosis: an example of cytokine mediated sickness behaviour?
Heesen, C. (2005) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp.2005.065805 · Cited by 343 · cited 1×
“and in individuals with inflammatory diseases such as multiple sclerosi”
BackgroundInflammatory biomarkers and fatigue during radiation therapy for breast and prostate cancer
Bower, J. E., Ganz, P. A., Tao, M. L., Hu, W., Belin, T. R., Sepah, S., Cole, S., & Aziz, N. (2009) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-08-2584 · Cited by 315 · cited 1×
“Patients with cancer often experience substantial increases in NF-κB inflammatory signalling owing to tumour-derived cytokines, the effects of cancer treatment (for example, radiation and chemotherapy) on tissu”
BackgroundSelf-citationAn fMRI study of cytokine-induced depressed mood and social pain: The role of sex differences
Eisenberger, N. I., Inagaki, T. K., Rameson, L. T., Mashal, N. M., & Irwin, M. R. (2009) · NeuroImage · doi:10.1016/j.neuroimage.2009.04.040 · Cited by 313
Self-citationCole, S. W., Hawkley, L. C., Arevalo, J. M. G., & Cacioppo, J. T. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1014218108 · Cited by 306
Self-citationExercise Training and Plasma C‐Reactive Protein and Interleukin‐6 in Elderly People
Nicklas, B. J., Hsu, F., Brinkley, T. J., Church, T. S., Goodpaster, B. H., Kritchevsky, S. B., & Pahor, M. (2008) · Journal of the American Geriatrics Society · doi:10.1111/j.1532-5415.2008.01994.x · Cited by 296
Wong, M.-L., Dong, C., Maestre-Mesa, J., & Licinio, J. (2008) · Molecular Psychiatry · doi:10.1038/mp.2008.59 · Cited by 295
Capuron, L., Ravaud, A., & Dantzer, R. (2000) · Journal of Clinical Oncology · doi:10.1200/jco.2000.18.10.2143 · Cited by 293
Sleep loss activates cellular markers of inflammation: Sex differences
Irwin, M. R., Carrillo, C., & Olmstead, R. (2010) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2009.06.001 · Cited by 287
Self-citationLavretsky, H., Alstein, L. L., Olmstead, R. E., Ercoli, L. M., Riparetti-Brown, M., St. Cyr, N., & Irwin, M. R. (2011) · The American Journal of Geriatric Psychiatry · doi:10.1097/jgp.0b013e31820ee9ef · Cited by 268
Self-citationComputational identification of gene–social environment interaction at the human IL6 locus
Cole, S. W., Arevalo, J. M. G., Takahashi, R., Sloan, E. K., Lutgendorf, S. K., Sood, A. K., Sheridan, J. F., & Seeman, T. E. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0911515107 · Cited by 256 · cited 1×
“In addition to the global anti-inflammatory effect of glucocorticoids, a second neural pathway mediated by the SNS allows the CNS to 'steer' innate immune responses between pro-inflammatory and antiviral programme”
BackgroundSelf-citationImplications of immune-to-brain communication for sickness and pain
Watkins, L. R., & Maier, S. F. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.14.7710 · Cited by 250 · cited 1×
“Inflammatory regulation of behaviour Several molecular signalling pathways have been identified to convey peripheral pro-inflammatory and antiviral signals into the brai”
BackgroundCole, S. W., Korin, Y. D., Fahey, J. L., & Zack, J. A. (1998) · The Journal of Immunology · doi:10.4049/jimmunol.161.2.610 · Cited by 228
Self-citationDose-dependent effects of endotoxin on human sleep
Mullington, J., Korth, C., Hermann, D. M., Orth, A., Galanos, C., Holsboer, F., & Pollmächer, T. (2000) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.2000.278.4.r947 · Cited by 226
Engler, H., Bailey, M. T., Engler, A., & Sheridan, J. F. (2004) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2003.11.011 · Cited by 209 · cited 1×
“and experimental analyses of repeated social threat in animal models (such as encountering an aggressive intruder”
BackgroundGoebel, M. U., Mills, P. J., Irwin, M. R., & Ziegler, M. G. (2000) · Psychosomatic Medicine · doi:10.1097/00006842-200007000-00019 · Cited by 189
Self-citationMonk, J. P., Phillips, G., Waite, R., Kuhn, J., Schaaf, L. J., Otterson, G. A., Guttridge, D., Rhoades, C., Shah, M., Criswell, T., et al. (2006) · Journal of Clinical Oncology · doi:10.1200/jco.2005.04.2838 · Cited by 179
Davis, M. C., Zautra, A. J., Younger, J., Motivala, S. J., Attrep, J., & Irwin, M. R. (2008) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2007.06.013 · Cited by 177
Self-citationComplex Systems Science in Biomedicine
Deisboeck, T. S., & Kresh, J. Y. (2006) · Springer eBooks · doi:10.1007/978-0-387-33532-2 · Cited by 171
Sloan, E. K., Capitanio, J. P., Tarara, R. P., Mendoza, S. P., Mason, W. A., & Cole, S. W. (2007) · Journal of Neuroscience · doi:10.1523/jneurosci.1247-07.2007 · Cited by 170
Self-citationBower, J. E., Ganz, P. A., Irwin, M. R., Arevalo, J. M. G., & Cole, S. W. (2010) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2010.09.010 · Cited by 169
Self-citationRaison, C. L., Lowry, C. A., & Rook, G. A. W. (2010) · Archives of General Psychiatry · doi:10.1001/archgenpsychiatry.2010.161 · Cited by 169
Bower, J. E., Ganz, P. A., Aziz, N., Olmstead, R. E., Irwin, M. R., & Cole, S. W. (2006) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2006.08.001 · Cited by 169
Self-citationGeographical genomics of human leukocyte gene expression variation in southern Morocco
Idaghdour, Y., Czika, W., Shianna, K. V., Lee, S. H., Visscher, P. M., Martin, H. C., Miclaus, K., Jadallah, S. J., Goldstein, D. B., Wolfinger, R. D., et al. (2010) · Nature Genetics · doi:10.1038/ng.495 · Cited by 151 · cited 1×
“These include: environmentally dependent variations in the basal transcriptome of unstimulated immune cell”
BackgroundCytokine gene polymorphisms and fatigue in breast cancer survivors: Early findings
Collado-Hidalgo, A., Bower, J. E., Ganz, P. A., Irwin, M. R., & Cole, S. W. (2008) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2008.05.009 · Cited by 137 · cited 1×
“Fatigue in breast cancer survivors is also particularly elevated among patients with IL1B , IL6 or TNF polymorphisms that cause high-level expression of the respective cytokine”
BackgroundSelf-citationGrebe, K. M., Takeda, K., Hickman, H. D., Bailey, A. M., Embry, A. C., Bennink, J. R., & Yewdell, J. W. (2010) · The Journal of Immunology · doi:10.4049/jimmunol.0903395 · Cited by 130
Genome-wide transcriptional profiling linked to social class in asthma
Chen, E., Miller, G. E., Walker, H. A., Arevalo, J. M., Sung, C. Y., & Cole, S. W. (2008) · Thorax · doi:10.1136/thx.2007.095091 · Cited by 118 · cited 1×
“People confronting long-term social adversities — such as the mortal illness of a spouse, low socio-economic status, post-traumatic stress disorder or long-term social isolation — have repeatedly been found to show increased expression of pro-inflammatory immune response genes, despite the presence of stable or elevat…”
BackgroundSelf-citationRaison, C. L., Rye, D. B., Woolwine, B. J., Vogt, G. J., Bautista, B. M., Spivey, J. R., & Miller, A. H. (2010) · Biological Psychiatry · doi:10.1016/j.biopsych.2010.04.019 · Cited by 116
Mitigating Cellular Inflammation in Older Adults: A Randomized Controlled Trial of Tai Chi Chih
Irwin, M. R., & Olmstead, R. E. (2011) · American Journal of Geriatric Psychiatry · doi:10.1097/jgp.0b013e3182330fd3 · Cited by 107
Self-citationSex differences in monocyte expression of IL-6: role of autonomic mechanisms
O'Connor, M., Motivala, S. J., Valladares, E. M., Olmstead, R., & Irwin, M. R. (2007) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00752.2006 · Cited by 101
Self-citationSleep depth and fatigue: Role of cellular inflammatory activation
Thomas, K. S., Motivala, S. J., Olmstead, R., & Irwin, M. R. (2010) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2010.07.245 · Cited by 91 · cited 1×
“Pro-inflammatory gene expression can induce profound fatigue during waking hour”
BackgroundSelf-citationOmenn, G. S. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0906198106 · Cited by 78
Fatigue in primary Sjögren’s syndrome – A link to sickness behaviour in animals?
Harboe, E., Tjensvoll, A. B., Vefring, H. K., Gøransson, L. G., Kvaløy, J. T., & Omdal, R. (2009) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2009.06.151 · Cited by 76
Benedetti, F., Lucca, A., Brambilla, F., Colombo, C., & Smeraldi, E. (2002) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/s0278-5846(02)00255-5 · Cited by 73
Collado-Hidalgo, A., Sung, C., & Cole, S. (2006) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2006.01.005 · Cited by 69 · cited 1×
“In addition to the global anti-inflammatory effect of glucocorticoids, a second neural pathway mediated by the SNS allows the CNS to 'steer' innate immune responses between pro-inflammatory and antiviral programme”
BackgroundSelf-citationCho, H. J., Seeman, T. E., Bower, J. E., Kiefe, C. I., & Irwin, M. R. (2009) · Biological Psychiatry · doi:10.1016/j.biopsych.2009.06.008 · Cited by 59 · cited 1×
“Clinical studies have documented links between inflammation-related biomarkers and the development of fatigue both in healthy older adult”
BackgroundSelf-citationTumor Necrosis Factor Antagonism Normalizes Rapid Eye Movement Sleep in Alcohol Dependence
Irwin, M. R., Olmstead, R., Valladares, E. M., Breen, E. C., & Ehlers, C. L. (2009) · Biological Psychiatry · doi:10.1016/j.biopsych.2008.12.004 · Cited by 58 · cited 1×
“TNF antagonism can also normalize REM sleep levels (for example, in abstinent alcohol-dependent individuals, who have elevated amounts of REM sleep”
BackgroundSelf-citationRichlin, V. A., Arevalo, J. M. G., Zack, J. A., & Cole, S. W. (2003) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2003.08.001 · Cited by 49
Self-citationSleep and Immunity: Cytokine Pathways Linking Sleep and Health Outcomes
Motivala, S. J., & Irwin, M. R. (2007) · Current Directions in Psychological Science · doi:10.1111/j.1467-8721.2007.00468.x · Cited by 49
Self-citationImmunogenic dendritic cells primed by social defeat enhance adaptive immunity to influenza A virus
Powell, N. D., Mays, J. W., Bailey, M. T., Hanke, M. L., & Sheridan, J. F. (2010) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2010.07.243 · Cited by 36 · cited 1×
“, but recent findings suggest that this circuit originates with the innate immune syste”
BackgroundThe Complexity of Dynamic Host Networks
Cole, S. W. (2007) · Springer eBooks · doi:10.1007/978-0-387-33532-2_26 · Cited by 27
Self-citationFischer, G., & Wagner, B. (1983) · PubMed · Cited by 19
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The role of inflammation in depression: from evolutionary imperative to modern treatment target
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“The first effector pathway that regulates systemic inflammation is the SNS.”
BackgroundInfluentialSelf-citationIrwin, M. R., Olmstead, R., & Carroll, J. E. (2016) · Biological Psychiatry · doi:10.1016/j.biopsych.2015.05.014 · Cited by 2,085
“Sleep influences two primary effector systems, the hypothalamus-pituitary-adrenal axis and the sympathetic nervous system, which together shift the basal gene expression profile toward increased proinflammatory skewing (14,123).”
BackgroundSelf-citationCancer-related fatigue—mechanisms, risk factors, and treatments
Bower, J. E. (2014) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2014.127 · Cited by 1,666
Interoception and Mental Health: A Roadmap.
Khalsa, S. S., Adolphs, R., Cameron, O. G., Critchley, H. D., Davenport, P. W., Feinstein, J. S., Feusner, J. D., Garfinkel, S. N., Lane, R. D., Mehling, W. E., et al. (2018) · Biological psychiatry. Cognitive neuroscience and neuroimaging · doi:10.1016/j.bpsc.2017.12.004 · Cited by 1,453
Metadata
- Authors
- Irwin, M. R., & Cole, S. W.
- Affiliations
- University of California, Los Angeles (US)
- Corresponding author
- Irwin, Michael R.
- ORCID
- Irwin, Michael R.
- Venue
- Nature Reviews Immunology
- Published
- 2011-08-05
- Volume
- 11
- Issue
- 9
- Pages
- 625-632
- ISSN
- 1474-1733 (ISSN-L)
- 1474-1741
- PMC
- PMC3597082
- OpenAlex
- W2078619626
- Cited by
- 910
- References
- 85
- Citations by year
- 2026: 48 · 2025: 82 · 2024: 61 · 2023: 65 · 2022: 69 · 2021: 82 · 2020: 109 · 2019: 71 · 2018: 46 · 2017: 51 · 2016: 57 · 2015: 59 · 2014: 46 · 2013: 34 · 2012: 26
- FWCI
- 1.80
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature reviews. Immunology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Science Foundation Ireland
- National Institutes of Health (1ul1rr033176-01, UL1TR000124)
- National Institute on Aging (R01AG026364, R01AG034588, R37AG033590, P30AG028748, R01AG033590)
- National Heart, Lung, and Blood Institute (R01HL079955)
- National Institute of Mental Health (R01MH091352)
- National Institute on Drug Abuse (F31DA024904)
- National Cancer Institute (R01CA116778, R21CA138687, R01CA119159)
- National Center for Research Resources (UL1-RR-033176)
- National Center for Advancing Translational Sciences
- Topics
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- neuroimmune interactions, innate immunity, behavior, cytokines, stress, infection, neuropsychiatric disorders, chronic inflammation, chronic infection
- MeSH terms
- Central Nervous System, Endocrine System, Genes, MHC Class II, Humans, Immunity, Innate, Inflammation, Leukocytes, Neuroimmunomodulation, Signal Transduction, Cytokines
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