Loneliness: An Immunometabolic Syndrome
Abstract
:1. Introduction
- Inhibit the release of brain IL-1β, containing and reducing inflammation
- Increase the production of IL-6, consequently inducing hepatic acute-phase reactants, e.g., C-reactive protein (CRP), minimizing cellular damage
- Increase the release of macrophage migration inhibitory factor (MIF) by macrophages, and consequently:
- Reduce the sensitivity of immune cells to the anti-inflammatory effects of glucocorticoids,
- Promote tumor necrosis factor-alpha (TNF-α) release, sustaining low-grade inflammation in the setting of chronic stress [35].
2. Immunologic Factors
2.1. Inflammatory Cytokines
2.1.1. Endotoxin Trials
2.1.2. IL-6
2.1.3. TNF-α
2.1.4. IL-2 and IL-10
2.2. Growth Factors
2.2.1. VEGF
2.2.2. IGF-1
2.2.3. GM-CSF
2.3. Acute-Phase Reactants
2.3.1. CRP
2.3.2. Fibrinogen
2.3.3. Ferritin
2.4. Chemokines
2.4.1. MCP-1
2.4.2. MIF
2.5. Immunoglobulins
2.6. Antiviral Immunity
2.6.1. Interferons
2.6.2. Antibody Response against Viral Infection
2.6.3. Antibody Response against Vaccines
2.6.4. Behavioral Immunity against Viruses of Social Stigma
2.7. Immune Cells’ Number and Activity
2.8. Genetic Correlates of Immune Regulation
3. Metabolic Factors
3.1. Markers of HPA Function
3.1.1. Regulation of Glucocorticoids in Loneliness
3.1.2. Counter-Regulation of the Stress Circuitry in Loneliness
3.1.3. Measures of Cortisol in Loneliness
3.2. Markers of Glycemic Control
3.3. Markers of Lipid Metabolism
3.4. Indices of Weight Control and Body Composition
3.5. Meeting the Criteria for Metabolic Syndrome
3.6. Elements of Cardiovascular Function
3.7. Markers of Cognitive Function
3.8. Elements of Mental Health
3.9. Genetic Correlates of Metabolic Regulation
4. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Headings | Subheadings | Examples | |
---|---|---|---|
Immunologic factors | 1 | Inflammatory cytokines | IL-6, TNF-α, IL-2, IL-10 |
2 | Growth factors | VEGF, IGF-1, GM-CSF | |
3 | Acute-phase reactants | CRP, Fibrinogen, Ferritin | |
4 | Chemokines | MCP-1, MIF | |
5 | Immunoglobulins | IgA, IgG, IgM | |
6 | Antiviral immunity | ||
6.1. Interferons | Type 1 and 2 | ||
6.2. Antibody response against viral infection | CMV, EBV, HSV-1, HHV-6 | ||
6.3. Antibody response against vaccines | Influenza vaccination | ||
6.4. Behavioral immunity against viruses of social stigma | HIV, HCV, SARS-CoV-2 | ||
7 | Immune cell number and activity | WBC count, NK cell activity | |
8 | Genetic correlates of immune regulation | ||
Metabolic factors | 1 | Markers of HPA function | |
1.1. Regulation of glucocorticoids in loneliness | |||
1.2. Counter-regulation of the stress circuitry in loneliness | |||
1.3. Measures of cortisol in loneliness | |||
2 | Markers of glycemic control | HbA1c, FBS, T2DM | |
3 | Markers of lipid metabolism | Tg, Chol, HDL:Chol | |
4 | Indices of weight control and body composition | BMI, Obesity, Central adiposity, Anorexia | |
5 | Meeting the criteria for metabolic syndrome | ||
6 | Elements of cardiovascular function | BP, HR, CO, TPR | |
7 | Markers of cognitive function | BDNF, Amyloid beta | |
8 | Elements of mental health | Depression, Schizophrenia, Sleep quality | |
9 | Genetic correlates of metabolic regulation | NR3C1, NF-κB/Rel |
Immunologic Factors | Relation to Loneliness | |||
---|---|---|---|---|
+ | − | No/NS | ||
Inflammatory cytokines | IL-6 | [43,66,67,68,69,70,71,72,73] | [78,81,93,120] | |
TNF-α | [43,66] | [66] | ||
IFNs | [64,79] | |||
IL-1α | [121] | |||
IL-1β | [66] | |||
IL-10 | [79] | |||
IL-1RA | [68] | [93] | ||
IL-2 | [78] (NS) | |||
Growth factors | VEGF | [81] | ||
IGF-1 | [83] | |||
GM-CSF | [80] (NS) | |||
Adhesion molecules | sICAM-1 | [72] | ||
Acute-phase reactants | CRP | [42,70,72,86] | [67,89,97] | |
Fibrinogen | [70,88] | [89] | [67,90] | |
Ferritin | [86] | |||
Chemokines | MCP-1 | [68,93] | ||
MIF | [95] | |||
Immunoglobulins | Plasma IgA | [97] | [96] | |
Salivary IgA | [99] | [97] | ||
Plasma IgG | [96] | [97] | ||
Plasma IgM | [96] | [97] | ||
Antibody against viruses | CMV | [101,103] | ||
EBV | [101] | [103] | ||
HSV-1 | [101,102] | |||
SIV | [64] | |||
Antibody response against vaccines | Influenza immunization | [105] | ||
Low dose rDNA hepatitis B vaccine | [122] | |||
Immune cell activity | NK cell activity | [88] | [97,99] | |
Lymphocyte functions | [99] | |||
Genetic correlates of immune regulation | Genes supporting mature B lymphocyte function | [42] | ||
Genes in type I interferon response | [42] | |||
Genes involved in immune activation, transcription control, and cell proliferation | [42] |
Metabolic Factors | Relation to Loneliness | |||
---|---|---|---|---|
+ | − | No/NS | ||
Markers of HPA function | Cortisol output post-stress | [93] | [95] | |
Salivary waking cortisol levels | [88,124,149] | [68,69,95] | [21,79] | |
Plasma cortisol | [105,124,192] | |||
Cortisol awakening response (CAR) | [124,149] | |||
Cortisol diurnal slope (DS) | [149,150] | [124] | ||
Cortisol AUCG | [149] | |||
DHEAs | [78] | |||
Markers of glycemic control | T2DM | [153,154] | ||
Hyperglycemia | [26] | |||
HbA1c | [155,156] | [157,158,159] | ||
FBS | [25](p = 0.07) | |||
AKT activity | [193] | |||
“Glycemic success” in T2DM | [161] | |||
fear of hypoglycaemia in adults with T1DM | [194] | |||
Markers of lipid metabolism | Tg | [26,162,163] | [25,157] | |
Total Chol | [157] | |||
HDL Chol | [26,162] | [25] | ||
Non-HDL Chol | [157] | |||
LDL Chol (LDL-C) | [157] | |||
Percentage of EPA and DHA in erythrocyte membrane | [164] | |||
Indices of weight control and body composition | BMI | [78,156,163,165] | [21,157] | |
Obesity | [25,162,166,167,168,169] | |||
Body fat | [163] | |||
Anorexia of aging | [172] | |||
Insufficient dietary intake and trace metals levels in the elderly | [173,174,175,176] | |||
Disturbed levels of appetite-relevant hormones | [102] | |||
Increased food consumption | [102] | |||
Higher intake of sugary beverages | [171] | |||
Meeting the criteria for metabolic syndrome | Metabolic burden | [156,166] | ||
Metabolic syndrome | [25,26,162] | [195] | ||
Metabolic disorders | [163] | |||
Elements of cardiovascular function | Hypertension | [26,155] | [25] | |
Systolic BP | [21,69,78,157,177] | [158] | ||
Diastolic BP | [21,88] | [78,157,158] | ||
Heart rate (HR) | [21] | |||
Cardiac output (CO) | [21] | |||
Total peripheral resistance (TPR) | [21] | |||
Cardiac contractility | [21] | |||
Autonomic cardiac control | [178] | |||
Coronary heart disease (CHD) | [22] | |||
Stroke | [22] | |||
Cardiovascular disease | [153,163,179] | |||
NYHA class | [182] | |||
Cardiovascular mortality | [180,181] | |||
Markers of cognitive function | Dementia | [23] | ||
Elevated cortical amyloid burden | [183] | |||
BDNF | [184] | [196] | ||
Allopregnanolone | [184] (hypothesis) | |||
Structural Brain Correlates | [185] | |||
Elements of mental health | Depression | [26,88,182,186] | [78] | |
Pain | [103] | |||
Fatigue | [103] | |||
Schizophrenia | [155] | |||
Diagnosis of drug abuse/dependence | [155] | |||
Number of drugs used | [155] | |||
Trouble adjusting to hassles | [79] | |||
Mental health outcome | [24,105,163] | |||
Sleep quality | [21,46,88,105] | |||
Health behavior | [166,177,188] | [21] | ||
Recreational drug use | [21] | |||
Physical activity | [189] | |||
Genetic correlates of metabolic regulation | Genes involving anti-inflammatory GREs | [42,190] | ||
Oxidative stress | [190] | |||
Genes involving response elements for pro-inflammatory NF-κB/Rel transcription factors | [42] | |||
Genes associated with DNA methylation and epigenetic changes | [191] | |||
BDNF Val66Met polymorphism | [197] | |||
All-cause mortality | [24,27,28] |
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Pourriyahi, H.; Yazdanpanah, N.; Saghazadeh, A.; Rezaei, N. Loneliness: An Immunometabolic Syndrome. Int. J. Environ. Res. Public Health 2021, 18, 12162. https://doi.org/10.3390/ijerph182212162
Pourriyahi H, Yazdanpanah N, Saghazadeh A, Rezaei N. Loneliness: An Immunometabolic Syndrome. International Journal of Environmental Research and Public Health. 2021; 18(22):12162. https://doi.org/10.3390/ijerph182212162
Chicago/Turabian StylePourriyahi, Homa, Niloufar Yazdanpanah, Amene Saghazadeh, and Nima Rezaei. 2021. "Loneliness: An Immunometabolic Syndrome" International Journal of Environmental Research and Public Health 18, no. 22: 12162. https://doi.org/10.3390/ijerph182212162
APA StylePourriyahi, H., Yazdanpanah, N., Saghazadeh, A., & Rezaei, N. (2021). Loneliness: An Immunometabolic Syndrome. International Journal of Environmental Research and Public Health, 18(22), 12162. https://doi.org/10.3390/ijerph182212162