Conceptual development of the immune system as a sixth sense
Abstract
Understanding how and why the immune and nervous systems communicate in a bidirectional pathway has been fundamental to the development of the psychoneuroimmunology (PNI) field. This review will discuss some of the pivotal results that found the nervous and immune systems use a common chemical language for intra and inter-system communication. Specifically the nervous and immune systems produce a common set of peptide and nonpeptide neurotransmitters and cytokines that provides a common repertoire of receptors and ligands between the two systems. These studies led to the concept that through the sharing of ligands and receptors the immune system could serve as a sixth sense to detect things the body cannot otherwise hear, see, smell, taste or touch. Pathogens, tumors, and allergens are detected with great sensitivity and specificity by the immune system. As a sixth sense the immune system is a means to signal and mobilize the body to respond to these types of challenges. The paper will also review in a chronological manner some of the PNI-related studies important to validating the sixth sense concept. Finally, the review will suggest ways to apply the new found knowledge of the sixth sense to understanding a placebo effect and developing new therapeutic approaches for treatment of human diseases.
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A recent systematic review reported an increase in transforming growth factor-β as the most consistent cytokine finding across ME/CFS studies.
“a recent systematic review reported an increase in transforming growth factor (TGF)-β as the most consistent finding across studies (59).”
From The Sleep-Immune Crosstalk in Health and Disease (2019) · cites this paper as [59]
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- Authors
- Blalock, J. E., & Smith, E. M.
- Affiliations
- University of Alabama at Birmingham (US)
- The University of Texas Medical Branch at Galveston (US)
- Corresponding author
- Smith, Eric M.
- Venue
- Brain, Behavior, and Immunity
- Publisher
- Elsevier BV
- Published
- 2007-01
- Volume
- 21
- Issue
- 1
- Pages
- 23-33
- ISSN
- 0889-1591 (ISSN-L)
- OpenAlex
- W2038803905
- Cited by
- 153
- References
- 43
- Citations by year
- 2026: 4 · 2025: 9 · 2024: 3 · 2023: 5 · 2022: 6 · 2021: 6 · 2020: 7 · 2019: 10 · 2018: 8 · 2017: 4 · 2016: 12 · 2015: 4 · 2014: 7 · 2013: 12 · 2012: 8
- FWCI
- 4.33
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Brain Behavior and Immunity (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Heart, Lung, and Blood Institute (R01HL077783, HL077783, R01HL068806, HL-68806)
- National Institute of Neurological Disorders and Stroke (NS41495, R01NS041495)
- Topics
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Neurology › Vagus Nerve Stimulation Research
- Keywords
- psychoneuroimmunology, neurotransmitters, cytokines, peptide neurotransmitters, placebo effect, treatment options
- MeSH terms
- Animals, Forecasting, Humans, Neuroendocrinology, Neurosecretory Systems, Psychoneuroimmunology, Research Design, Neuroimmunomodulation, Signal Transduction, History, 20th Century, History, 21st Century, Mice
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