Targeting the Oxytocinergic System: A Possible Pharmacological Strategy for the Treatment of Inflammation Occurring in Different Chronic Diseases
Abstract
:1. Introduction
1.1. Inflammation
1.2. The Oxytocinergic System
2. Oxytocin–Glia Communication
3. Oxytocin Signaling and Inflammation Occurring in Chronic Diseases
3.1. Neurological Diseases
3.2. Inflammatory Pain
3.3. Obesity and Diabetes
3.4. Gastrointestinal Inflammatory Diseases
3.5. Cardiovascular Diseases
3.6. COVID-19
4. Conclusions
Author Contributions
Funding
Conflicts of Interest
Abbreviations
CNS | central nervous system |
PLC | phospholipase C |
Ca2+ | calcium |
LPS | lipopolysaccharide |
ROS | Reactive oxygen species |
GSH | glutathione |
NPC | neural progenitor cells |
MAPK | mitogen-activated protein kinase |
ERK | extracellular signal-regulated kinase |
GFAP | glial fibrillar acidic protein |
CD | cluster of differentiation |
CNPase | 2′,3′-Cyclic-nucleotide 3′-phosphodiesterase |
TGF | transforming growth factor |
AQP | aquaporin |
TNF | tumor necrosis factor |
IL | interleukin |
COX | cyclooxygenase |
iNOS | inducible nitric oxide synthase |
Iba | ionized calcium-binding adapter molecule |
TLR | toll-like receptor |
NF | nuclear factor |
BDNF | brain-derived neurotrophic factor |
IFN | interferon |
PSD | postsynaptic density protein |
CRP | C-reactive protein |
CFA | complete Freund adjuvant |
DPP | dipeptidyl-peptidase |
ASD | autism spectrum disorder |
T2DM | type 2 diabetes mellitus |
DIO | diet-induced obesity |
GI | gastrointestinal |
IBD | inflammatory bowel diseases |
OXYR-KO | oxytocin receptor knockout |
TNBS | 2,4,6-trinitrobenzene sulfonic acid |
NEC | necrotizing enterocolitis |
CVD | cardiovascular disease |
HF | heart failure |
I/R | ischemia/reperfusion |
COVID | coronavirus disease |
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Depression | ||||
Subjects | Targets | Analysis | Effect | Reference |
Mice model of maternal separation | Hippocampus | i.c.v. oxytocin administration | Attenuated depressive-like behavior, Restored GSH, decreased ROS Decreased TNF-α, IL-1β, and TLR-4 | [63] |
Mice subjected chemotherapy | Hippocampus | i.c.v. oxytocin administration | Attenuated depressive-like behavior Decreased IL-6 | [88] |
Adolescent rats from postpartum depressive dams | Hippocampus | i.p. oxytocin administration | Increased social investigation, stimulated neurogenesis Decreased neuroinflammation (IL-6:IL-10 ratio) | [89] |
ASD | ||||
Subjects | Targets | Analysis | Effect | Reference |
Autistic male patients | Plasma | Endogenous oxytocin levels | Negative correlation between oxytocin and IFN-γ-induced protein-16 | [101] |
Autistic mice from valproate treated dams | Hippocampus Amygdala | i.n. oxytocin administration | Improved anxiety-, depressive-like, and social behaviors, Decreased IL-6, IL-1β, TNF-α Decreased ROS, restored GSH | [102] |
Hippocampus Cortex | Decreased Iba1 | |||
OXYR-KO mice | Brain | Endogenous oxytocin levels | Decreased PSD95, increased Iba1 | [70] |
Inflammatory Pain | ||||
Subjects | Targets | Analysis | Effect | Reference |
Rat model of peripheral painful inflammatory sensitization | Spinal cord | Optogenetic stimulation of oxytocin parvocellular neurons | Attenuated nociceptive transmission | [108] |
Rat model of peripheral painful inflammatory sensitization | Spinal cord | i.p. administration of selective oxytocin receptor agonist LIT-001 | Increased mechanical and thermal pain threshold | [109] |
Rat model of bone cancer | Spinal cord | i.t. oxytocin administration | Increased mechanical and thermal pain thresholds Decreased IL-1β, TNF-α, and TLR-4 | [110] |
Rat model of carrageenan-induced inflammation | Spinal cord | s.c. oxytocin administration | Increased mechanical and thermal pain thresholds | [43] |
At the injection site of carrageenan (hind paw) | Decreased local edema and neutrophil infiltration | |||
Rat model of carrageenan-induced inflammation | Spinal cord | i.t. oxytocin administration | Increased mechanical and thermal pain thresholds | [111] |
Obesity and Diabetes | ||||
Subjects | Targets | Analysis | Effect | Reference |
apoE−/− mice | Adipose tissue | s.c. oxytocin infusion | Decreased IL-6 | [112] |
ob/ob mice | Adipose tissue | s.c. oxytocin infusion | Decreased body weight gain | [113] |
Decreased macrophages infiltration | ||||
db/db mice | Adipose tissue | s.c. oxytocin infusion | Decreased adipocyte size Decreased macrophages’ infiltration, IL-6, and TNF-α Increased adiponectin | [114] |
Plasma | Decreased plasma serum amyloid A | |||
Mice C57bl/6JRj | Bone marrow-derived macrophages | Stimulation with oxytocin | Decreased TNF-α secretion | [115] |
DIO mice | s.c. oxytocin infusion | Decreased body weight and improved glucose tolerance | ||
Macrophages | Decreased TNF-α secretion | |||
Human MetS subject | Plasma | Endogenous oxytocin levels | Decreased TNF-α Increased IL-10 and IL-6 | [116] |
Gastrointestinal Tract Pathologies | ||||
Subjects | Targets | Analysis | Effect | Reference |
Rat model of colitis | Colon | i.v. oxytocin + secretin administration | Prevented transmission of inflammation-evoked signals to PVN, AMY, and piriform cortex Decreased inflammatory infiltration Decreased TNF-α and INF-γ | [117] |
Model of colitis induced in OXYR-KO mice | Intestine | s.c. oxytocin administration | Decreased levels of TNF- α and CCR5 | [37] |
Isolated newborn rat gut villi | rat gut villi | Oxytocin colostrum level | Increased the inhibition of NF-kB pathway | [118] |
Murine NEC model | Intestine | Peripheral oxytocin administration | Decreased transcription of proinflammatory chemokines and cytokines Increased transcription of anti-inflammatory gene products | [119] |
Rat model of gastric ulcer | stomach | i.p. administration of oxytocin receptor antagonist atosiban | Increased pro-inflammatory cytokine expressions | [120] |
Cardiovascular Diseases | ||||
Subjects | Targets | Analysis | Effect | Reference |
Human cells | Primary aortic endothelial cells | Stimulation with oxytocin | Attenuated atherosclerotic lesion formation Decreased IL-6 | [121] |
Rat model of myocardial infarction | Infarcted cardiac areas | s.c. oxytocin infusion | Decreased macrophages’, neutrophils’, and Lymphocytes’ infiltration Increased TGF-β Decreased IL-6, IL-1β, TNF-α | [122] |
apoE−/− mice | Aorta | s.c. oxytocin infusion | Decreased atherosclerosis | [112] |
Watanabe heritable hyperlipidemic rabbit | Aorta | s.c. oxytocin infusion | Decreased atherosclerosis | [123] |
Plasma | Decreased CRP | |||
Adipose tissue | Decreased IL-6 Increased adiponectin | |||
db/db mice | Cardiac tissue | s.c. oxytocin infusion | Decreased left ventricular weight and collagen volume fraction Decreased IL-6, IL-1β, NF-κB | [124] |
Rat model of heart failure | Cardiac tissue | Selective activation of PVN oxytocin neurons | Improved cardiac function Decreased fibrosis Decreased IL-1β | [125,126] |
Rat model of cardiomyopathy | Myocardial tissue | i.p. oxytocin administration | Improved tissue integrity Decreased oxidative stress, apoptosis, and inflammation | [127] |
Rat model of I/R | Cardiac tissue | i.p. oxytocin administration | Inhibited cardiac mast cells’ degranulation Decreased NF-κB and High Mobility Group Box-1 | [128] |
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Friuli, M.; Eramo, B.; Valenza, M.; Scuderi, C.; Provensi, G.; Romano, A. Targeting the Oxytocinergic System: A Possible Pharmacological Strategy for the Treatment of Inflammation Occurring in Different Chronic Diseases. Int. J. Mol. Sci. 2021, 22, 10250. https://doi.org/10.3390/ijms221910250
Friuli M, Eramo B, Valenza M, Scuderi C, Provensi G, Romano A. Targeting the Oxytocinergic System: A Possible Pharmacological Strategy for the Treatment of Inflammation Occurring in Different Chronic Diseases. International Journal of Molecular Sciences. 2021; 22(19):10250. https://doi.org/10.3390/ijms221910250
Chicago/Turabian StyleFriuli, Marzia, Barbara Eramo, Marta Valenza, Caterina Scuderi, Gustavo Provensi, and Adele Romano. 2021. "Targeting the Oxytocinergic System: A Possible Pharmacological Strategy for the Treatment of Inflammation Occurring in Different Chronic Diseases" International Journal of Molecular Sciences 22, no. 19: 10250. https://doi.org/10.3390/ijms221910250