Summary: The biochemical and electrophysiological interactions between the NERVOUS SYSTEM and IMMUNE SYSTEM.

Top Publications

  1. Bottasso O, Morales Montor J. Neuroimmunomodulation during infectious diseases: mechanisms, causes and consequences for the host. Neuroimmunomodulation. 2009;16:65-7 pubmed publisher
    In this special issue of Neuroimmunomodulation, the reader will find reviewed some of the hottest topics in the field of neuroendocrine-immune interactions, with emphasis on infectious diseases...
  2. Perry V. Contribution of systemic inflammation to chronic neurodegeneration. Acta Neuropathol. 2010;120:277-86 pubmed publisher
  3. Kokaia Z, Martino G, Schwartz M, Lindvall O. Cross-talk between neural stem cells and immune cells: the key to better brain repair?. Nat Neurosci. 2012;15:1078-87 pubmed publisher
    ..Better understanding of the dialog between NSPCs and innate and adaptive immune cells is crucial for further development of effective strategies for CNS repair. ..
  4. Morales I, Farías G, Maccioni R. Neuroimmunomodulation in the pathogenesis of Alzheimer's disease. Neuroimmunomodulation. 2010;17:202-4 pubmed publisher
  5. Ohman L, Simren M. Pathogenesis of IBS: role of inflammation, immunity and neuroimmune interactions. Nat Rev Gastroenterol Hepatol. 2010;7:163-73 pubmed publisher
    ..The link between immune alterations and severity of gastrointestinal symptoms and the positive effect of anti-inflammatory treatments in IBS further highlight the relevance of neuroimmune interactions in this condition. ..
  6. Bhat R, Steinman L. Innate and adaptive autoimmunity directed to the central nervous system. Neuron. 2009;64:123-32 pubmed publisher
  7. Capuron L, Miller A. Immune system to brain signaling: neuropsychopharmacological implications. Pharmacol Ther. 2011;130:226-38 pubmed publisher
  8. Verburg van Kemenade B, Ribeiro C, Chadzinska M. Neuroendocrine-immune interaction in fish: differential regulation of phagocyte activity by neuroendocrine factors. Gen Comp Endocrinol. 2011;172:31-8 pubmed publisher
    ..Inflammatory and microbicidal responses fight pathogens but may be detrimental to the host tissue. Neuroendocrine modulation may regulate inflammation to reach an optimum defense while preventing excessive host cell damage. ..
  9. Huston J, Tracey K. The pulse of inflammation: heart rate variability, the cholinergic anti-inflammatory pathway and implications for therapy. J Intern Med. 2011;269:45-53 pubmed publisher
    ..Favourable preclinical data support the possibility that nerve stimulators may be added to the future therapeutic armamentarium, possibly replacing some drugs to inhibit cytokines. ..

More Information


  1. Majoie H, Rijkers K, Berfelo M, Hulsman J, Myint A, Schwarz M, et al. Vagus nerve stimulation in refractory epilepsy: effects on pro- and anti-inflammatory cytokines in peripheral blood. Neuroimmunomodulation. 2011;18:52-6 pubmed publisher
    ..This results in: (1) a reduction of neurotoxic and an increase of neuroprotective kynurenine metabolites and (2) in the normalization of cortisol levels. ..
  2. Volpi C, Fazio F, Fallarino F. Targeting metabotropic glutamate receptors in neuroimmune communication. Neuropharmacology. 2012;63:501-6 pubmed publisher
    ..In this review we primarily focus on mGluRs and their role in the crosstalk between the central nervous and immune systems during neuroinflammation. ..
  3. De la Fuente M, Gimenez Llort L. Models of aging of neuroimmunomodulation: strategies for its improvement. Neuroimmunomodulation. 2010;17:213-6 pubmed publisher
    ..Therefore, they retard the aging process and seem to increase the longevity of the individuals. ..
  4. Reardon C, Duncan G, Brüstle A, Brenner D, Tusche M, Olofsson P, et al. Lymphocyte-derived ACh regulates local innate but not adaptive immunity. Proc Natl Acad Sci U S A. 2013;110:1410-5 pubmed publisher
    ..Despite this ability, ChAT(+) B cells were unable to suppress effector T-cell function in vivo. Therefore, ACh produced by lymphocytes has specific functions, with ChAT(+) B cells controlling the local recruitment of neutrophils. ..
  5. Kumar V, Sharma A. Is neuroimmunomodulation a future therapeutic approach for sepsis?. Int Immunopharmacol. 2010;10:9-17 pubmed publisher
    ..e. cholinergic pathway activated by vagus nerve stimulation, alpha- or beta-adrenergic receptor activation etc.) in sepsis. Hence neuroimmunomodulation can be a future approach to treat sepsis.
  6. Rosas Ballina M, Olofsson P, Ochani M, Valdés Ferrer S, Levine Y, Reardon C, et al. Acetylcholine-synthesizing T cells relay neural signals in a vagus nerve circuit. Science. 2011;334:98-101 pubmed publisher
    ..Thus, action potentials originating in the vagus nerve regulate T cells, which in turn produce the neurotransmitter, acetylcholine, required to control innate immune responses. ..
  7. Zunszain P, Hepgul N, Pariante C. Inflammation and depression. Curr Top Behav Neurosci. 2013;14:135-51 pubmed publisher
    ..Further understanding of pathways involved is still needed. This will be vital for the identification of new drug targets and preventative strategies. ..
  8. Ribeiro Machado M, Dias Da Silva V. Autonomic neuroimmunomodulation in chagasic cardiomyopathy. Exp Physiol. 2012;97:1151-60 pubmed publisher
    ..The pathogenic implications of these potential neural immune manipulations are also discussed. ..
  9. Maes M, Kubera M, Obuchowiczwa E, GOEHLER L, Brzeszcz J. Depression's multiple comorbidities explained by (neuro)inflammatory and oxidative & nitrosative stress pathways. Neuro Endocrinol Lett. 2011;32:7-24 pubmed
    ..This shows that depression belongs to the spectrum of inflammatory and degenerative disorders. ..
  10. Carpentier P, Palmer T. Immune influence on adult neural stem cell regulation and function. Neuron. 2009;64:79-92 pubmed publisher
  11. Arck P, Paus R. From the brain-skin connection: the neuroendocrine-immune misalliance of stress and itch. Neuroimmunomodulation. 2006;13:347-56 pubmed
  12. Singh P, Singal P. Morphine-induced neuroimmunomodulation in murine visceral leishmaniasis: the role(s) of cytokines and nitric oxide. J Neuroimmune Pharmacol. 2007;2:338-51 pubmed
    ..These results thus demonstrate the implications of opiate abuse on the efficacy assessment of antileishmanial drugs and vaccines, and on the reactivation of latent VL in areas where both drug abuse and VL are rampant. ..
  13. Ortega E, Giraldo E, Hinchado M, Martín L, Garcia J, De la Fuente M. Neuroimmunomodulation during exercise: role of catecholamines as 'stress mediator' and/or 'danger signal' for the innate immune response. Neuroimmunomodulation. 2007;14:206-12 pubmed
    Exercise-induced neuroimmunomodulation is clearly accepted today...
  14. Barone L, Colicchio G, Policicchio D, Di Clemente F, Di Monaco A, Meglio M, et al. Effect of vagal nerve stimulation on systemic inflammation and cardiac autonomic function in patients with refractory epilepsy. Neuroimmunomodulation. 2007;14:331-6 pubmed publisher
    ..Our data in epileptic patients without cardiovascular disease failed to show a significant effect of left VNS on cardiac autonomic function and on systemic inflammation at short-term follow-up. ..
  15. Griffiths M, Neal J, Gasque P. Innate immunity and protective neuroinflammation: new emphasis on the role of neuroimmune regulatory proteins. Int Rev Neurobiol. 2007;82:29-55 pubmed
    ..Moreover, NIRegs have direct beneficial effects on neurogenesis and contributing to brain tissue remodeling. ..
  16. Popovich P, Longbrake E. Can the immune system be harnessed to repair the CNS?. Nat Rev Neurosci. 2008;9:481-93 pubmed publisher
    ..Here, we evaluate the controversies in the field and discuss the remaining scientific challenges that are associated with enhancing immune function in the CNS to treat neurological diseases. ..
  17. De la Fuente M. Role of neuroimmunomodulation in aging. Neuroimmunomodulation. 2008;15:213-23 pubmed publisher
    ..In the context of neuroimmunomodulation, it is now accepted that the age-related impairment of immune functions is the cause of the increased ..
  18. Tracey K. Reflex control of immunity. Nat Rev Immunol. 2009;9:418-28 pubmed publisher
    ..It might be possible to develop therapeutics that target neural networks for the treatment of inflammatory disorders. ..
  19. Ysrraelit M, Gaitán M, Lopez A, Correale J. Impaired hypothalamic-pituitary-adrenal axis activity in patients with multiple sclerosis. Neurology. 2008;71:1948-54 pubmed publisher
  20. Irwin M, Miller A. Depressive disorders and immunity: 20 years of progress and discovery. Brain Behav Immun. 2007;21:374-83 pubmed
    ..Moreover, the work has served to instantiate brain-immune interactions as an essential component in psychiatric and medical co-morbidities and their impact on health and illness. ..
  21. Tian L, Rauvala H, Gahmberg C. Neuronal regulation of immune responses in the central nervous system. Trends Immunol. 2009;30:91-9 pubmed publisher
    ..In addition, we specifically deal with the immune functions of neuronal cell adhesion molecules, many of which are key modulators of neuronal synaptic formation and plasticity. ..
  22. de Moura E, Lisboa P, Passos M. Neonatal programming of neuroimmunomodulation--role of adipocytokines and neuropeptides. Neuroimmunomodulation. 2008;15:176-88 pubmed publisher
  23. Franco R, Pacheco R, Lluis C, Ahern G, O Connell P. The emergence of neurotransmitters as immune modulators. Trends Immunol. 2007;28:400-7 pubmed
    ..Current and future developments in understanding the cross-talk between the immune and nervous systems will probably identify new avenues for treating immune-mediated diseases using agonists or antagonists of neurotransmitter receptors. ..
  24. Silva J, Lopes A, Talbot J, Cecílio N, Rossato M, Silva R, et al. Neuroimmune-Glia Interactions in the Sensory Ganglia Account for the Development of Acute Herpetic Neuralgia. J Neurosci. 2017;37:6408-6422 pubmed publisher
    ..1 in satellite glial cells. This study elucidates novel mechanisms involved in the genesis of acute herpetic neuralgia and open new avenues for its control. ..
  25. Kanwar A, Bhansali A, Parsad D. Evaluation of hypothalamic-pituitary-adrenal axis in patients with atopic dermatitis. Indian J Dermatol Venereol Leprol. 2011;77:288-93 pubmed publisher
    ..The disease activity rather than the use of topical corticosteroids is responsible for the low basal levels in patients with severe AD. ..
  26. Olofsson P, Rosas Ballina M, Levine Y, Tracey K. Rethinking inflammation: neural circuits in the regulation of immunity. Immunol Rev. 2012;248:188-204 pubmed publisher
    ..Here, we review recent progress in the understanding of the inflammatory reflex and discuss potential therapeutic implications of current findings in this evolving field. ..
  27. McCusker R, Kelley K. Immune-neural connections: how the immune system's response to infectious agents influences behavior. J Exp Biol. 2013;216:84-98 pubmed publisher
    ..Collectively, these data are consistent with the notion that the immune system communicates with the brain to regulate behavior in a way that is consistent with animal survival...
  28. Lu Y, Gu Y, Ding X, Wang J, Chen J, Miao C. Intracellular Ca2+ homeostasis and JAK1/STAT3 pathway are involved in the protective effect of propofol on BV2 microglia against hypoxia-induced inflammation and apoptosis. PLoS ONE. 2017;12:e0178098 pubmed publisher
    ..Propofol could protect BV2 microglia from hypoxia-induced inflammation and apoptosis. The potential mechanisms may involve the maintaining of intracellular Ca2+ homeostasis and the activation of JAK1/STAT3 pathway. ..
  29. Jiang J, Peng Y, Qiu Y, Wang J. [Effect of the endogenous catecholamines synthesized by lymphocytes on T cell proliferation]. Zhongguo Ying Yong Sheng Li Xue Za Zhi. 2009;25:81-5 pubmed
    ..The endogenous CAs synthesized by lymphocytes can inhibit T cell proliferation and the inhibition of T cells by the CAs is mediated predominantly by beta2-AR on the lymphocytes. ..
  30. Northrop N, Northrup N, Yamamoto B. Neuroimmune pharmacology from a neuroscience perspective. J Neuroimmune Pharmacol. 2011;6:10-9 pubmed publisher
    ..The emerging field of neuroimmune pharmacology exemplifies this interdisciplinary approach and has facilitated the study of basic cellular and molecular events and disease states and opens avenues for novel therapies. ..
  31. Siniscalchi M, Sasso R, Pepe A, Dimatteo S, Vallortigara G, Quaranta A. Catecholamine plasma levels following immune stimulation with rabies vaccine in dogs selected for their paw preferences. Neurosci Lett. 2010;476:142-5 pubmed publisher
  32. Mantelli F, Micera A, Sacchetti M, Bonini S. Neurogenic inflammation of the ocular surface. Curr Opin Allergy Clin Immunol. 2010;10:498-504 pubmed publisher
  33. Tracey K. Understanding immunity requires more than immunology. Nat Immunol. 2010;11:561-4 pubmed publisher
  34. Gonzalez Rey E, Ganea D, Delgado M. Neuropeptides: keeping the balance between pathogen immunity and immune tolerance. Curr Opin Pharmacol. 2010;10:473-81 pubmed publisher
    ..Finally, we discuss how a physiologically functional neuropeptide system contributes to general health and how neuropeptides educate our immune system to be tolerant. ..
  35. Matzinger P, Kamala T. Tissue-based class control: the other side of tolerance. Nat Rev Immunol. 2011;11:221-30 pubmed publisher
  36. Yuan G, Jia Z, Yang H, Wu S, Gao H, Wei C, et al. Comfortable lifestyle-induced imbalance of neuro-endocrine-immunity network: a possible mechanism of vascular endothelial dysfunction. Chin J Integr Med. 2010;16:54-60 pubmed publisher
  37. Leclerc J, Lampert A, Diller M, Immergluck J, Doré S. Prostaglandin E2 EP2 receptor deletion attenuates intracerebral hemorrhage-induced brain injury and improves functional recovery. ASN Neuro. 2015;7: pubmed publisher
    ..Targeting the EP2 G protein-coupled receptor may represent a new therapeutic avenue for the treatment of hemorrhagic stroke. ..
  38. Li R, Zhang Z, Peng M, Wu Y, Zhang J, Wang C, et al. Postoperative impairment of cognitive function in old mice: a possible role for neuroinflammation mediated by HMGB1, S100B, and RAGE. J Surg Res. 2013;185:815-24 pubmed publisher
    ..These data suggest that HMGB1, S100B, and RAGE signaling modulate the hippocampal inflammatory response and might play key roles in surgery-induced cognitive decline. ..
  39. Gonzalez Rey E. Keeping the balance between immune tolerance and pathogen immunity with endogenous neuropeptides. Neuroimmunomodulation. 2010;17:161-4 pubmed publisher
    ..From a physiological point of view, neuropeptides play a critical role in the innate-adaptive immune cross talk that allows survival. ..
  40. Nava Castro K, Hernández Bello R, Muñiz Hernández S, Camacho Arroyo I, Morales Montor J. Sex steroids, immune system, and parasitic infections: facts and hypotheses. Ann N Y Acad Sci. 2012;1262:16-26 pubmed publisher
  41. Idova G, Alperina E, Cheido M. Contribution of brain dopamine, serotonin and opioid receptors in the mechanisms of neuroimmunomodulation: evidence from pharmacological analysis. Int Immunopharmacol. 2012;12:618-25 pubmed publisher
    ..The presented data may have implications for the treatment of emotional stress and mental disorders associated with changes in activity of brain DA, 5-HT, opioid systems and their receptor function as well as immune reactivity. ..
  42. Zhao N, Zhang W, Guo Y, Jia H, Zha Q, Liu Z, et al. Effects on neuroendocrinoimmune network of Lizhong Pill in the reserpine induced rats with spleen deficiency in traditional Chinese medicine. J Ethnopharmacol. 2011;133:454-9 pubmed publisher
  43. Threlkeld S, Lynch J, Lynch K, Sadowska G, Banks W, Stonestreet B. Ovine proinflammatory cytokines cross the murine blood-brain barrier by a common saturable transport mechanism. Neuroimmunomodulation. 2010;17:405-10 pubmed publisher
    ..Knowledge of species-conserved BBB transport mechanisms may facilitate the development of novel animal models of central nervous system pathogenesis. ..
  44. Cao B, Han X, Huang Y, Qiu Y, Peng Y. The hypothalamus mediates the effect of cerebellar fastigial nuclear glutamatergic neurons on humoral immunity. Neuro Endocrinol Lett. 2012;33:393-400 pubmed
    ..Cerebellar FN glutamatergic neurons participate in modulation of humoral immunity and this effect is mediated by the hypothalamus via FN-hypothalamic glutamatergic transmission. ..
  45. Mazzoccoli G, Tarquini R, Durfort T, Francois J. Chronodisruption in lung cancer and possible therapeutic approaches. Biomed Pharmacother. 2011;65:500-8 pubmed publisher
  46. Ferrero M. Purinoceptors in inflammation: potential as anti-inflammatory therapeutic targets. Front Biosci (Landmark Ed). 2011;16:2172-86 pubmed
  47. Undem B, Taylor Clark T. Mechanisms underlying the neuronal-based symptoms of allergy. J Allergy Clin Immunol. 2014;133:1521-34 pubmed publisher
    ..A better understanding of these processes might lead to novel therapeutic strategies aimed at limiting the suffering of those with allergies. ..
  48. Solomos A, Rall G. Get It through Your Thick Head: Emerging Principles in Neuroimmunology and Neurovirology Redefine Central Nervous System "Immune Privilege". ACS Chem Neurosci. 2016;7:435-41 pubmed publisher
    ..Collectively, these attributes demand a re-evaluation of immunity in the brain: not privileged, but distinct. ..
  49. Correale J, Farez M. The impact of parasite infections on the course of multiple sclerosis. J Neuroimmunol. 2011;233:6-11 pubmed publisher
    ..These new observations on parasite infections associated to MS indicate that parasite regulation of host immunity can alter the course of MS...
  50. Deak T, Kudinova A, Lovelock D, Gibb B, Hennessy M. A multispecies approach for understanding neuroimmune mechanisms of stress. Dialogues Clin Neurosci. 2017;19:37-53 pubmed
  51. Cardenas S, Scuri M, Samsell L, Ducatman B, Bejarano P, Auais A, et al. Neurotrophic and neuroimmune responses to early-life Pseudomonas aeruginosa infection in rat lungs. Am J Physiol Lung Cell Mol Physiol. 2010;299:L334-44 pubmed publisher
    ..Our data suggest that neurogenic-mediated immunoinflammatory mechanisms play important roles in airway inflammation and hyperreactivity associated with P. aeruginosa when infection occurs early in life. ..
  52. Gately C, Podbielska M, Counihan T, Hennessy M, Leahy T, Moran A, et al. Invariant Natural Killer T-cell anergy to endogenous myelin acetyl-glycolipids in multiple sclerosis. J Neuroimmunol. 2013;259:1-7 pubmed publisher
    ..In marked contrast, MS patients failed to respond to FMCs or to ?-GalCer stimulation indicating an anergic response. We propose that myelin-derived FMC glycolipids stimulate iNKT-cell responses in vivo and this is blocked in MS. ..
  53. Mallimo E, Ansonoff M, Pintar J, Kusnecov A. Role of opioid receptor like-1 receptor in modulation of endocrine, immunological, and behavioral responses to the T-cell superantigen staphylococcal enterotoxin A. J Neuroimmunol. 2010;218:48-56 pubmed publisher
    ..These results suggest differential requirements for ORL(1) in the mediation of neuroimmune effects exerted at different times after an immune challenge. ..