Cytokines-Biogenesis and Their Role in Human Breast Milk and Determination

Cytokines play a huge role in many biological processes. Their production, release and interactions are subject to a very complex mechanism. Cytokines are produced by all types of cells, they function very differently and they are characterized by synergism in action, antagonism, and aggregation activity, opposing action of one cytokine, overlapping activity, induction of another cytokine, inhibition of cytokine synthesis at the mRNA level as well as autoregulation-stimulation or inhibition of own production. The predominance of pro-inflammatory cytokines leads to a systemic inflammatory response, and anti-inflammatory-to an anti-inflammatory response. They regulate the organism’s immune response and protect it against sudden disturbances in homeostasis. The synthesis and activity of cytokines are influenced by the central nervous system through the endocrine system (pituitary gland, adrenal glands).

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Focal intra-colon cooling reduces organ injury and systemic inflammation after REBOA management of lethal hemorrhage in rats

Scientific Reports ◽

10.1038/s41598-021-93064-4 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Awadhesh K. Arya ◽

Kurt Hu ◽

Lalita Subedi ◽

Tieluo Li ◽

Bingren Hu

Keyword(s):

Inflammatory Response ◽

Inflammatory Cytokines ◽

Troponin I ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Balloon Catheter ◽

Organ Injury ◽

Upper Body ◽

Anti Inflammatory ◽

Pro Inflammatory Cytokines

AbstractResuscitative endovascular balloon occlusion of the aorta (REBOA) is a lifesaving maneuver for the management of lethal torso hemorrhage. However, its prolonged use leads to distal organ ischemia–reperfusion injury (IRI) and systemic inflammatory response syndrome (SIRS). The objective of this study is to investigate the blood-based biomarkers of IRI and SIRS and the efficacy of direct intestinal cooling in the prevention of IRI and SIRS. A rat lethal hemorrhage model was produced by bleeding 50% of the total blood volume. A balloon catheter was inserted into the aorta for the implementation of REBOA. A novel TransRectal Intra-Colon (TRIC) device was placed in the descending colon and activated from 10 min after the bleeding to maintain the intra-colon temperature at 37 °C (TRIC37°C group) or 12 °C (TRIC12°C group) for 270 min. The upper body temperature was maintained at as close to 37 °C as possible in both groups. Blood samples were collected before hemorrhage and after REBOA. The organ injury biomarkers and inflammatory cytokines were evaluated by ELISA method. Blood based organ injury biomarkers (endotoxin, creatinine, AST, FABP1/L-FABP, cardiac troponin I, and FABP2/I-FABP) were all drastically increased in TRIC37°C group after REBOA. TRIC12°C significantly downregulated these increased organ injury biomarkers. Plasma levels of pro-inflammatory cytokines TNF-α, IL-1b, and IL-17F were also drastically increased in TRIC37°C group after REBOA. TRIC12°C significantly downregulated the pro-inflammatory cytokines. In contrast, TRIC12°C significantly upregulated the levels of anti-inflammatory cytokines IL-4 and IL-10 after REBOA. Amazingly, the mortality rate was 100% in TRIC37°C group whereas 0% in TRIC12°C group after REBOA. Directly cooling the intestine offered exceptional protection of the abdominal organs from IRI and SIRS, switched from a harmful pro-inflammatory to a reparative anti-inflammatory response, and mitigated mortality in the rat model of REBOA management of lethal hemorrhage.

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Anti-inflammatory therapy in an ovine model of fetal hypoxia induced by single umbilical artery ligation

Reproduction Fertility and Development ◽

10.1071/rd10110 ◽

2011 ◽

Vol 23 (2) ◽

pp. 346 ◽

Cited By ~ 12

Author(s):

Micka C. Bertucci ◽

Jan M. Loose ◽

Euan M. Wallace ◽

Graham Jenkin ◽

Suzanne L. Miller

Keyword(s):

Inflammatory Response ◽

Intrauterine Growth Restriction ◽

Umbilical Artery ◽

Blood Gases ◽

Fetal Hypoxia ◽

Single Umbilical Artery ◽

Artery Ligation ◽

Pregnant Sheep ◽

Anti Inflammatory ◽

Pro Inflammatory Cytokines

Perinatal morbidity and mortality are significantly higher in pregnancies complicated by chronic hypoxia and intrauterine growth restriction (IUGR). Clinically, placental insufficiency and IUGR are strongly associated with a fetoplacental inflammatory response. To explore this further, hypoxia was induced in one fetus in twin-bearing pregnant sheep (n = 9) by performing single umbilical artery ligation (SUAL) at 110 days gestation. Five ewes were administered the anti-inflammatory drug sulfasalazine (SSZ) daily, beginning 24 h before surgery. Fetal blood gases and inflammatory markers were examined. In both SSZ- and placebo-treated ewes, SUAL fetuses were hypoxic and growth-restricted at 1 week (P < 0.05). A fetoplacental inflammatory response was observed in SUAL pregnancies, with elevated pro-inflammatory cytokines, activin A and prostaglandin E2. SSZ did not mitigate this inflammatory response. It is concluded that SUAL induces fetal hypoxia and a fetoplacental inflammatory response and that SSZ does not improve oxygenation or reduce inflammation. Further studies to explore whether alternative anti-inflammatory treatments may improve IUGR outcomes are warranted.

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Polymethoxyflavone Apigenin-Trimethylether Suppresses LPS-Induced Inflammatory Response in Nontransformed Porcine Intestinal Cell Line IPEC-J2

Oxidative Medicine and Cellular Longevity ◽

10.1155/2015/673847 ◽

2015 ◽

Vol 2015 ◽

pp. 1-10 ◽

Cited By ~ 14

Author(s):

Orsolya Farkas ◽

Orsolya Palócz ◽

Erzsébet Pászti-Gere ◽

Péter Gálfi

Keyword(s):

Gene Expression ◽

Inflammatory Response ◽

Intestinal Inflammation ◽

Mrna Level ◽

Intestinal Cell ◽

Amplex Red ◽

Cox 2 ◽

Anti Inflammatory ◽

Inflammatory Effect

Thein vitroanti-inflammatory effect of apigenin and its trimethylated analogue (apigenin-trimethylether) has been investigated in order to evaluate whether these flavonoids could attenuate LPS-induced inflammation in IPEC-J2 non-transformed intestinal epithelial cells. Levels of IL-6, IL-8, TNF-α, and COX-2 mRNA were measured as a marker of inflammatory response. The extracellular H2O2level in IPEC-J2 cells was also monitored by Amplex Red assay. Our data revealed that both compounds had significant lowering effect on the inflammatory response. Apigenin (at 25 μM) significantly decreased gene expression of IL-6 in LPS-treated cells, while apigenin-trimethylether in the same concentration did not influence IL-6 mRNA level. Both apigenin and apigenin-trimethylether reduced IL-8 gene expression significantly. TNF-αmRNA level was decreased by apigenin-trimethylether, which was not influenced by apigenin. Treatment with both flavonoids caused significant reduction in the mRNA level of COX-2, but the anti-inflammatory effect of the methylated analogue was more effective than the unmethylated one. Furthermore, both flavonoids reduced significantly the level of extracellular H2O2compared to the control cells. In conclusion, the methylated apigenin analogue could avoid LPS-induced intestinal inflammation and it could be applied in the future as an effective anti-inflammatory compound.

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Electroacupuncture Improves M2 Microglia Polarization and Glia Anti-inflammation of Hippocampus in Alzheimer’s Disease

Frontiers in Neuroscience ◽

10.3389/fnins.2021.689629 ◽

2021 ◽

Vol 15 ◽

Author(s):

Lushuang Xie ◽

Yi Liu ◽

Ning Zhang ◽

Chenyu Li ◽

Aaron F. Sandhu ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Inflammatory Response ◽

Inflammatory Cytokines ◽

Inflammatory Cytokine ◽

Cytokine Expression ◽

Tnf Α ◽

Microglia Polarization ◽

Anti Inflammatory ◽

Pro Inflammatory Cytokines

Background: Alzheimer’s disease (AD) is a neurodegenerative disease characterized by loss of recognition and memory. Neuroinflammation plays pivotal roles in the pathology of AD and affects the progression of the disease. Astrocyte and microglia, as main immune executors in the central nervous system (CNS), participate into the inflammatory response in AD. Glia polarize into different phenotypes during neurodegeneration. Pro-inflammatory glia produce cytokines (IL-1β, TNF-α, and IL-6) resulting into debris aggregates and neurotoxicity. Anti-inflammatory phenotypes produce cytokines (IL-4 and IL-10) to release the inflammation. Electroacupuncture is a useful treatment that has been found to slow the neurodegeneration in animals through experimentation and in humans through clinical trials. The aim of this study was to uncover the mechanisms of glia activation, microglia polarization, and cytokine secretion regulated by electroacupuncture as a treatment for AD.Methods: Twenty male Sprague–Dawley (SD) rats were randomly divided into four groups: Control group (Control), Normal saline group (NS), AD group (AD), and Electroacupuncture group (Acupuncture). The AD and Acupuncture groups were bilaterally injected with Aβ1–42 into the CA1 field of the hippocampus. The Acupuncture group received electroacupuncture stimulation on the acupoint “Baihui” (GV20) for 6 days per week for a total of 3 weeks. The Morris Water Maze (MWM) was used to evaluate learning and memory capacity. Immunofluorescence was used to stain GFAP and Iba1 of the DG and CA1 in the hippocampus, which, respectively, expressed the activation of astrocyte and microglia. The M1 microglia marker, inducible nitric oxide synthase (iNOS), and M2 marker Arginase 1 (Arg1) were used to analyze the polarization of microglia. The pro-inflammatory cytokines (IL-1β, TNF-α, and IL-6), anti-inflammatory cytokines (IL-4 and IL-10), and pathway-molecules (p65 and Stat6) were tested to analyze the glia inflammatory response by immunofluorescence and polymerase chain reaction (PCR).Results: The MWM results showed that electroacupuncture improves the escape latency time and the swimming distance of AD rats. The number of GFAP and Iba1 cells significantly increased in AD rats, but electroacupuncture decreased the cells. The iNOS-positive cells were significantly increased in AD, and electroacupuncture decreased the positive cells. Electroacupuncture elevated Arg1-positive cells in AD rats. Electroacupuncture decreased the glia pro-inflammatory cytokine expression and increased the anti-inflammatory cytokine expression in AD rats. Furthermore, electroacupuncture inhibited the NF-κB pathway molecule (p65) while raising the Stat6 pathway molecule (Stat6).Conclusion: These results provide evidence that electroacupuncture improves the recognition abilities and memory of AD rats. Electroacupuncture inhibits the activation of glia and polarizes microglia toward the M2 phenotype. Electroacupuncture decreased the pro-inflammatory cytokines (IL-1β, TNF-α, and IL-6) and increased the anti-inflammatory cytokines (IL-4 and IL-10). Furthermore, electroacupuncture affects the immune responses through inhibition of NF-κB pathway but activation of Stat6 pathway.

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Role of the immune response in the pathogenesis of Alzheimer’s disease and possibilities of anti-inflammatory therapy

Neurology Bulletin ◽

10.17816/nb34654 ◽

2021 ◽

Vol LII (3) ◽

pp. 55-62

Author(s):

Sergey V. Vorobev ◽

Andrey Yu. Emelin ◽

Raisa N. Kuznetsova ◽

Igor V. Kudryavtsev

Keyword(s):

Inflammatory Cytokines ◽

Therapeutic Potential ◽

Main Role ◽

Markers Of Inflammation ◽

Alternative Hypotheses ◽

The Central Nervous System ◽

Anti Inflammatory ◽

T Helpers ◽

Pro Inflammatory Cytokines

In modern scientific society several alternative hypotheses for the formation of Alzheimers disease are considered, proposed on the basis of data obtained as a result of research. In almost any of them, the development of an immuno-inflammatory response is discussed as one of the main pathogenic mechanisms of the disease. It was found that the development of neurodegeneration is accompanied by the accumulation of pro-inflammatory cytokines and other markers of inflammation in the peripheral blood and brain tissues. At the same time, the obtained results suggest that the main role in pathogenesis may be played by T-helpers of the Th17 population that can penetrate the blood-brain barrier. In addition, microglia, which is the main immune-presenting component of the central nervous system, and astrocytes, which are capable of excessive production of pro- inflammatory cytokines and regulation of -amyloid clearance, are considered as key components in these reactions. Based on these data, attempts are being made to develop drugs that have an anti-inflammatory effect and can positively influence the dynamics of the disease. The initial results obtained in some cases demonstrate a certain positive effect, which suggests that there is a therapeutic potential for this type of therapy.

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Characterization, Cytotoxicity and Anti-Inflammatory Effect Evaluation of Nanocapsules Containing Nicotine

Bioengineering ◽

10.3390/bioengineering8110172 ◽

2021 ◽

Vol 8 (11) ◽

pp. 172

Author(s):

Carolina Landau Albrecht ◽

Laura Elena Sperling ◽

Daikelly Iglesias Braghirolli ◽

Patricia Pranke

Keyword(s):

Encapsulation Efficiency ◽

Release Profile ◽

In Vitro Tests ◽

Effect Evaluation ◽

System 2 ◽

The Central Nervous System ◽

Anti Inflammatory ◽

Pro Inflammatory Cytokines ◽

Inflammatory Effect

(1) Background: Nanotechnology is an emerging field that can be applied in the biomedical area. In this study, Eudragit nanocapsules (NCs) containing nicotine were produced. Nicotine is the main alkaloid found in tobacco and has anti-inflammatory properties. NCs containing nicotine may be used as an adjuvant therapy in the treatment of inflammation in the central nervous system. (2) Methods: Nanocapsules were prepared by the interfacial deposition of the pre-formed polymer method and characterized in terms of zeta potential, diameter, polydispersity index, pH, encapsulation efficiency (EE), stability and sustained release profile. In vitro tests with the PC12 cell line were performed, such as MTT, LIVE/DEAD and ELISA assays, to verify their cytotoxic and anti-inflammatory effects. (3) Results: The nanocapsules presented satisfactory values of the characterization parameters; however, poor encapsulation was obtained for nicotine (8.17% ± 0.47). The in vitro tests showed that the treatment with nanocapsules reduced cell viability, which suggests that the Eudragit or the amount of polymer on top of the cells may be detrimental to them, as the cells were able to survive when treated with bulk nicotine. ELISA showed an increment in the expression of IL-6 and IL-1β, corroborating the hypothesis that NCs were toxic to the cells because of the increase in the levels of these pro-inflammatory cytokines. (4) Conclusions: This study demonstrates that NCs of Eudragit present toxicity. It is therefore necessary to improve NC formulation to obtain better values for the encapsulation efficiency and reduce toxicity of these nanodevices.

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The effective regulation of pro- and anti-inflammatory cytokines induced by combination of PA-MSHA and BPIFB1 in initiation of innate immune responses

Open Medicine ◽

10.1515/med-2017-0044 ◽

2017 ◽

Vol 12 (1) ◽

pp. 299-307 ◽

Cited By ~ 1

Author(s):

Weiqiang Zhou ◽

Zhiwen Duan ◽

Biao Yang ◽

Chunling Xiao

Keyword(s):

Inflammatory Response ◽

Immune Responses ◽

Inflammatory Cytokines ◽

Late Phase ◽

Upper Airway ◽

Innate Immune ◽

Antibody Array ◽

Innate Immune Responses ◽

Anti Inflammatory ◽

Pro Inflammatory Cytokines

AbstractPA-MSHA and BPIFB1 play especially important roles in triggering innate immune responses by inducing production of pro- or anti-inflammatory cytokines in the oral cavity and upper airway. We found that PA-MSHA had a strong ability to activate pro-inflammatory cytokines such as IL-1β, IL-6 and TNF-α. However, BPIFB1 alone did not express a directly inductive effect. With incubation of PA-MSHA and BPIFB1, the combination can activate the CD14/TLR4/MyD88 complex and induce secretion of subsequent downstream cytokines. We used a proteome profiler antibody array to evaluate the phosphokinases status with PA-MSHA and BPIFB1 treatment. The results showed that the activation of MAPK, STAT, and PI-3K pathways is involved in PA-MSHA-BPIFB1 treatment, and that the related pathways control the secretion of targeting cytokines in the downstream. When we assessed the content changes of cytokines, we found that PA-MSHA-BPIFB1 treatment increased the production of pro-inflammatory cytokines in the early phase of treatment and induced the increase of IL-4 in the late phase. Our observations suggest that PA-MSHA-BPIFB1 stimulates the release of pro-inflammatory cytokines, and thereby initiates the innate immune system against inflammation. Meanwhile, the gradual release of anti-inflammatory cytokine IL-4 by PA-MSHA-BPIFB1 can also regulate the degree of inflammatory response; thus the host can effectively resist the environmental risks, but also manipulate inflammatory response in an appropriate and adjustable manner.

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Recent Advances in the Anti-Inflammatory Activity of Plant-Derived Alkaloid Rhynchophylline in Neurological and Cardiovascular Diseases

Pharmaceutics ◽

10.3390/pharmaceutics13081170 ◽

2021 ◽

Vol 13 (8) ◽

pp. 1170

Author(s):

Rajeswari Gopal Geetha ◽

Surya Ramachandran

Keyword(s):

Cardiovascular System ◽

Indole Alkaloid ◽

Underlying Mechanism ◽

Inflammatory Activity ◽

Protective Properties ◽

The Central Nervous System ◽

Anti Inflammatory ◽

Aggregation Activity ◽

The Brain ◽

Early Atherosclerosis

Rhynchophylline (Rhy) is a plant-derived indole alkaloid isolated from Uncaria species. Both the plant and the alkaloid possess numerous protective properties such as anti-inflammatory, neuroprotective, anti-hypertensive, anti-rhythmic, and sedative effects. Several studies support the significance of the anti-inflammatory activity of the plant as an underlying mechanism for most of the pharmacological activities of the alkaloid. Rhy is effective in protecting both the central nervous system and cardiovascular system. Cerebro-cardiovascular disease primarily occurs due to changes in lifestyle habits. Many previous studies have highlighted the significance of Rhy in modulating calcium channels and potassium channels, thereby protecting the brain from neurodegenerative diseases and related effects. Rhy also has anticoagulation and anti-platelet aggregation activity. Although Rhy has displayed its role in protecting the cardiovascular system, very little is explored about its intervention in early atherosclerosis. Extensive studies are required to understand the cardioprotective effects of Rhye. This review summarized and discussed the various pharmacological effects of Rhy in neuro- and cardioprotection and in particular the relevance of Rhy in preventing early atherosclerosis using Rhy-loaded nanoparticles.

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