Sterile Inflammation of Brain, due to Activation of Innate Immunity, as a Culprit in Psychiatric Disorders
Open accessAbstract
Evidence has accumulated that the occurrence of psychiatric disorders is related to chronic inflammation. In support of this linkage, changes in the levels of circulating pro-inflammatory cytokines and chemokines in the peripheral blood (PB) of psychiatric patients as well as correlations between chronic inflammatory processes and psychiatric disorders have been described. Furthermore, an inflammatory process known as "sterile inflammation" when initiated directly in brain tissue may trigger the onset of psychoses. In this review, we will present the hypothesis that prolonged or chronic activation of the complement cascade (ComC) directly triggers inflammation in the brain and affects the proper function of this organ. Based on the current literature and our own work on mechanisms activating the ComC we hypothesize that inflammation in the brain is initiated by the mannan-binding lectin pathway of ComC activation. This activation is triggered by an increase in brain tissue of danger-associated molecular pattern (DAMP) mediators, including extracellular ATP and high-mobility group box 1 (HMGB1) protein, which are recognized by circulating pattern-recognition receptors, including mannan-binding lectin (MBL), that activate the ComC. On the other hand, this process is controlled by the anti-inflammatory action of heme oxygenase 1 (HO-1). In this review, we will try to connect changes in the release of DAMPs in the brain with inflammatory processes triggered by the innate immunity involving activation of the ComC as well as the inflammation-limiting effects of the anti-inflammatory HO-1 pathway. We will also discuss parallel observations that during ComC activation subsets of stem cells are mobilized into PB from bone marrow that are potentially involved in repair mechanisms.
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Recent evidence indicates that the occurrence of psychiatric disorders in patients is linked to "sterile" inflammation of the brain that may be initiated locally by some stressors affecting nervous tissue or occurs due to a systemic inflammation process.
“Recent evidence indicates that the occurrence of psychiatric disorders in patients is linked to “sterile” inflammation of the brain that may be initiated locally by some stressors affecting nervous tissue or occurs due to a systemic inflammation process [17, 46].”
From Hyperactivation of P2X7 receptors as a culprit of COVID-19 neuropathology (2021) · cites this paper as [46]
Some reported anti-inflammatory treatment strategies ameliorate neurodegeneration.
“This may also explain, why some reported anti-inflammatory treatment strategies ameliorate neurodegeneration [17, 46].”
From Hyperactivation of P2X7 receptors as a culprit of COVID-19 neuropathology (2021) · cites this paper as [46]
Several inflammatory mediators and markers are detected in the peripheral blood of patients with psychiatric and neurodegenerative disorders, which could worsen prognoses for COVID-19 outcome.
“This is supported by the observation that several inflammatory mediators and markers are detected in the peripheral blood of patients with psychiatric and neurodegenerative disorders [17, 46], which could worsen prognoses for COVID-19 outcome.”
From Hyperactivation of P2X7 receptors as a culprit of COVID-19 neuropathology (2021) · cites this paper as [46]
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- Authors
- Ratajczak, M. Z., Pedziwiatr, D., Cymer, M., Kucia, M., Kucharska-Mazur, J., & Samochowiec, J.
- Affiliations
- University of Louisville (US)
- Medical University of Warsaw (PL)
- Pomeranian Medical University (PL)
- Corresponding author
- Ratajczak, Mariusz Z.
- Venue
- Frontiers in Psychiatry
- Publisher
- Frontiers Media SA
- Published
- 2018-02-28
- Volume
- 9
- Pages
- 60-60
- ISSN
- 1664-0640 (ISSN-L)
- PMC
- PMC5835766
- OpenAlex
- W2794126485
- Cited by
- 27
- References
- 38
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 5 · 2023: 3 · 2022: 3 · 2021: 4 · 2020: 6 · 2019: 2 · 2018: 2
- FWCI
- 0.31
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Frontiers in Psychiatry (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institutes of Health (R01 DK074720, R01HL112788)
- Narodowe Centrum Nauki (OPUS grant DEC-2016/23/B/NZ3/03157)
- Topics
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Immunology and Microbiology › Immunology › Complement system in diseases
- Keywords
- complement activation, damage-associated molecular patterns, extracellular ATP, HMGB1, heme oxygenase-1, innate immunity, inflammatory cytokines, chemokines, psychosis, mental illness, stem cell mobilization, neuroinflammation
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