Dysbalance of cytokines in schizophrenia and strategies for restoration of immune functions

2020 ◽  
pp. 1-4
Keyword(s):  
Monoclonal Antibodies ◽  
Immune System ◽  
Inflammatory Cytokines ◽  
Cumulative Effect ◽  
Theoretical Explanation ◽  
Psychotropic Medications ◽  
Immune Functions ◽  
Human Macrophages ◽  
Individualized Approach ◽  
Pro Inflammatory Cytokines

We discuss the cumulative effect of different cytokines in veterans with schizophrenia. Previously we reported that the chemoattractant G-CSF, MCP, MDC and GRO, which activates human macrophages, monocytes, neutrophils and basophils that these factors were significantly increased compared to control subjects and also that levels NF-γ and IL-17 and Il-2 were significantly decreased as compared to controls. Based on these results we hypothesize that the immune system with schizophrenia is trying to restore the balance of their immune system by reducing the amounts of pro-inflammatory cytokines and increasing the amounts of anti-inflammatory and regulating cytokines. We decided to use an unorthodox approach by clustering the cytokines in four groups according to their predominant functions and analyzing the effect of cumulative amounts of cytokines in each group. This hypothetical approach provided theoretical explanation about the changes of cytokines in patients with schizophrenia. We suggest an individualized approach for treatment of psychosis in patients with schizophrenia by augmenting psychotropic medications with the help of monoclonal antibodies which block the excessive amounts of specific proinflammatory cytokines.

scholarly journals A pronounced uterine pro-inflammatory response at parturition is an ancient feature in mammals

2017 ◽  
Vol 284 (1865) ◽  
pp. 20171694 ◽  
Author(s):  
Victoria L. Hansen ◽  
Lauren S. Faber ◽  
Ali A. Salehpoor ◽  
Robert D. Miller
Keyword(s):  
Immune System ◽  
Inflammatory Response ◽  
Inflammatory Cytokines ◽  
Immune Regulation ◽  
Monodelphis Domestica ◽  
Immune Gene ◽  
Invasive Placenta ◽  
Gene Transcripts ◽  
Pro Inflammatory Cytokines

Regulating maternal immunity is necessary for successful human pregnancy. Whether this is needed in mammals with less invasive placentation is subject to debate. Indeed, the short gestation times in marsupials have been hypothesized to be due to a lack of immune regulation during pregnancy. Alternatively, the maternal marsupial immune system may be unstimulated in the absence of a highly invasive placenta. Transcripts encoding pro-inflammatory cytokines were found to be overrepresented in the whole uterine transcriptome at terminal pregnancy in the opossum, Monodelphis domestica . To investigate this further, immune gene transcripts were quantified throughout opossum gestation. Transcripts encoding pro-inflammatory cytokines remained relatively low during pre- and peri-attachment pregnancy stages. Levels dramatically increased late in gestation, peaking within 12 h prior to parturition. These results mirror the spike of inflammation seen at eutherian parturition but not at attachment or implantation. Our results are consistent with the role of pro-inflammatory cytokines at parturition being an ancient and conserved birth mechanism in therian mammals.

scholarly journals Estrogen receptor α phosphorylated at Ser216 confers inflammatory function to mouse microglia

2019 ◽  
Author(s):  
Sawako Shindo ◽  
Shih-Heng Chen ◽  
Saki Gotoh ◽  
Kosuke Yokobori ◽  
Hao Hu ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Inflammatory Cytokines ◽  
Estrogen Receptor Α ◽  
Microglia Activation ◽  
Immune Functions ◽  
Protein Levels ◽  
Brain Extracts ◽  
Anti Inflammatory ◽  
The Brain ◽  
Pro Inflammatory Cytokines

Abstract Background Estrogen has been suggested to regulate anti-inflammatory signaling in brain microglia through estrogen receptor α (ERα), the only resident immune cells of the brain. The mechanism of how ERα regulates is not well understood. Previously, ERα is phosphorylated at Ser216 in mouse neutrophils, regulating their infiltration into the uterus. Therefore, ERα has now been examined as to its phosphorylation in microglia to regulate their inflammatory functions.MethodsAn antibody against an anti-phospho-S216 peptide of ERα (αP-S216) was used for double immunofluorescence staining to detect to ERα in cultured microglia. A knock-in (KI) mouse line bearing the phosphorylation-blocked ERα mutation S216A (ERα KI) was generated to examine whether this phosphorylation regulate immune functions of microglia.ResultsPhosphorylated ERα at Ser216 was present in microglia but not astrocytes. Staining with an anti-Iba-1 antibody showed that microglia activation was augmented in substantial nigra of ERα KI brains. Lipopolysaccharide (LPS) treatments aggravated microglia activation in ERα KI brains, pro-inflammatory cytokines were increased while anti-inflammatory cytokines were decreased at mRNA and protein levels in whole brain extracts. These increases and decreases of cytokine proteins were also observed in LPS-treated microglia cultured from brains of ERα KI neonates. FACS analysis revealed that ERα KI mutation increased number of IL-6 producing microglia and apoptosis. ERα KI mice decreased motor connection ability in Rotarod tests.ConclusionsBlocking of Ser216 phosphorylation aggravated microglia activation and inflammation of mouse brain, thus confirming that phosphorylated ERα exerts anti-inflammatory functions. ERα KI mice enable us to further investigate the mechanism by which phosphorylated ERα regulates brain immunity and inflammation.

Stable expression ratios of five pyroptosis-inducing cytokines in the spleen and thymus of mice showed potential immune regulation at the organ level

Lupus ◽  
2020 ◽  
Vol 29 (3) ◽  
pp. 290-302
Author(s):  
H Fan ◽  
S Zhang ◽  
N Li ◽  
P Fan ◽  
X Hu ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Immune System ◽  
Inflammatory Cytokines ◽  
Lupus Erythematosus ◽  
Immune Regulation ◽  
Interleukin 18 ◽  
Systemic Lupus ◽  
Tnf Α ◽  
Organ Level ◽  
Pro Inflammatory Cytokines

Background The immune system is one of the most complex regulatory systems in the body and is essential for the maintenance of homeostasis. Despite recent breakthroughs in immunology, the regulation of the immune system and the etiology of autoimmune diseases such as lupus remain unclear. Systemic lupus erythematosus is a systemic autoimmune disease with abnormally and inconsistently expressed pro-inflammatory cytokines. Pyroptosis is a pro-inflammatory form of programmed cell death that is associated with systemic lupus erythematosus. The thymus and spleen are important immune organs involved in systemic lupus erythematosus. Therefore, this study investigated the difference in expression of pyroptosis-inducing pro-inflammatory cytokines between the spleen and thymus in lupus model mice and in control mice, to describe immune regulation at the organ level. Objective To investigate differences in the expression of pyroptosis-inducing cytokines in the spleen and thymus and to explore immune regulatory networks at the organ level. Methods Two groups of lupus mice and two groups of control mice were utilized for this study. Using the thymus and spleen of experimental animals, mRNA expression levels of five pyroptosis-inducing cytokines (interleukin 1β, interleukin 18, NLRP3, caspase-1 and TNF-α) were determined via quantitative polymerase chain reaction. In addition, tissue distribution of these cytokines was investigated via immunohistochemistry. Results All five pyroptosis-inducing inflammatory cytokines showed higher expression in the spleen than in the thymus ( p < 0.05). Moreover, the spleen/thymus expression ratios of all five pyroptosis-inducing cytokines were not statistically different between the four experimental groups. Expression of all five cytokines exhibited a stable ratio (spleen/thymus ratios). This distinctive stable spleen/thymus ratio was consistent in all four experimental groups. The stable spleen/thymus ratios of the five inflammatory cytokines were as follows: interleukin 1β (2.02 ± 0.9), interleukin 18 (2.07 ± 1.06), caspase-1 (1.93 ± 0.66), NLRP3 (3.14 ± 1.61) and TNF-α (3.16 ± 1.36). Immunohistochemical analysis showed the cytokines were mainly expressed in the red pulp region of the spleen and the medullary region of the thymus, where immune-activated cells aggregated. Conclusion The stable spleen/thymus expression ratios of pyroptosis-inducing cytokines indicated that immune organs exhibit strictly regulated functions to maintain immune homeostasis and adapt to the environment.

Ovarian cancer and inflammation. Part 1. Pro-inflammatory cytokines.

2018 ◽  
Vol 8 (1) ◽  
pp. 194-201
Author(s):  
KM. Terlikowska ◽  
MA. Strzyż-Skalij ◽  
K. Kryński ◽  
M. Osmólska ◽  
Z. Łada ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Immune Response ◽  
Immune System ◽  
Immune Responses ◽  
Cause Of Death ◽  
Inflammatory Cytokines ◽  
Gynecologic Malignancies ◽  
Cancer Tumor ◽  
Cancer And Inflammation ◽  
Pro Inflammatory Cytokines

Ovarian cancer is the most threatening cause of death among gynecologic malignancies and represents the fifth leading cause of death from all cancers for women. Research reveals that ovarian cancer patients exhibit significant immune responses against the tumor. In this review of the current literature chiefly the interaction of ovarian cancer tumor cells and the immune system is discussed. There is increasingly growing evidence that pro-inflammatory cytokines are involved in intricate complex of mechanisms responsible for tumorigenesis, and delicate balance between pro- and anti-inflammatory cytokines is critical for the antitumor host immune response.

scholarly journals Theoretical Accounts of Gulf War Syndrome: From Environmental Toxins to Psychoneuroimmunology and Neurodegeneration

2002 ◽  
Vol 13 (3-4) ◽  
pp. 133-147 ◽  
Author(s):  
Eamonn Ferguson ◽  
Helen J. Cassaday
Keyword(s):  
Immune System ◽  
Inflammatory Cytokines ◽  
Interleukin 1 ◽  
Chronic Fatigue ◽  
Gulf War ◽  
T Helper 1 ◽  
Gulf War Syndrome ◽  
Fatigue Syndrome ◽  
Pro Inflammatory Cytokines ◽  
Specific Illness

Non-specific illness includes a wide variety of symptoms: behavioural (e.g., reduced food and water intake), cognitive (e.g., memory and concentration problems) and physiological (e.g., fever). This paper reviews evidence suggesting that such symptoms can be explained more parsimoniously as a single symptom cluster than as a set of separate illnesses such as Gulf War Syndrome (GWS) and chronic fatigue syndrome (CFS). This superordinate syndrome could have its biological basis in the activity of pro-inflammatory cytokines (in particular interleukin-1: IL-1), that give rise to what has become known as the ‘sickness response’. It is further argued that the persistence of non-specific illness in chronic conditions like GWS may be (in part) attributable to a bio-associative mechanism (Ferguson and Cassaday, 1999). In the case of GWS, physiological challenges could have produced a non-specific sickness response that became associated with smells (e.g., petrol), coincidentally experienced in the Persian Gulf. On returning to the home environment, these same smells would act as associative triggers for the maintenance of (conditioned) sickness responses. Such associative mechanisms could be mediated through the hypothalamus and limbic system via vagal nerve innervation and would provide an explanation for the persistence of a set of symptoms (e.g., fever) that should normally be short lived and self-limiting. We also present evidence that the pattern of symptoms produced by the pro-inflammatory cytokines reflects a shift in immune system functioning towards a (T-helper-1) Th1 profile. This position contrasts with other immunological accounts of GWS that suggest that the immune system demonstrates a shift to a Th2 (allergy) profile. Evidence pertaining to these two contrasting positions is reviewed.

scholarly journals Influence of environmental stress on immunity of swine

2016 ◽  
Vol 72 (10) ◽  
pp. 595-599
Author(s):  
Zygmunt Pejsak ◽  
Marian Truszczyński
Keyword(s):  
Immune System ◽  
Inflammatory Cytokines ◽  
Immune Cells ◽  
Management Practices ◽  
Acute Phase Proteins ◽  
Pathogenic Microorganisms ◽  
Environmental Management Practices ◽  
Chain Link ◽  
Microbial Environment ◽  
Pro Inflammatory Cytokines

This paper deals with pigs kept in environments, where they are exposed to a high number of pathogenic microbes and have reduced feed intake and growth, even when no obvious acute illness exists. According to the presented article this chronic drain on production is called immunologic stress. Sentinel immune cells (e.g. macrophages) supervise the diverse microbial environment by detecting pathogen – associated molecular patterns (PAMPs), which are molecules associated with groups of pathogens. The immune sentinels detect PAMPs mainly with Toll – like receptors (TLRs). Stimulation of macrophages through their TLRs leads to the synthesis and secretion of pro-inflammatory cytokines and prostaglandins, initiating the inflammatory response that recruits both immune molecules and circulating immune cells. Pro-inflammatory cytokines enable the immune system to communicate with other physiological systems. They rearrange the animal’s metabolic priorities, resulting in re-partitioning of nutrients away from productive processes towards responses that support the immune system. Thus, the immune system, through detection of PAMPs and production of pro-inflammatory cytokines, is the critical chain link connecting the pathogenic environment to productivity. The evaluation indicates, that at maintenance a healthy animal uses about 0,5-2% of the body’s lysine for leucocytes, antibodies and acute phase proteins. In the situation of contamination by pathogens of the environment the immune response is estimated to account for about 9% of the body’s lysine. Providing additional lysine in the diet does not improve the reduced growth of the pig, caused by immunologic stress as the result of contamination of the pig environment by pathogenic or facultatively pathogenic microorganisms. Thus, minimizing exposure to pathogenic microorganisms and providing sound environmental management practices is a high priority.

scholarly journals Ku70 and Ku80 participate in LPS-induced pro-inflammatory cytokines production in human macrophages and monocytes

Aging ◽  
2020 ◽  
Vol 12 (20) ◽  
pp. 20432-20444
Author(s):  
Hong Sun ◽  
Quan Li ◽  
Gang Yin ◽  
Xi Ding ◽  
Jing Xie
Keyword(s):  
Inflammatory Cytokines ◽  
Human Macrophages ◽  
Pro Inflammatory Cytokines
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