scholarly journals Evaluation of maternal-infant dyad inflammatory cytokines in pregnancies affected by maternal SARS-CoV-2 infection in early and late gestation.

2021 ◽  
Author(s):  
Elizabeth Taglauer ◽  
Yashoda Dhole ◽  
Jeffery Boateng ◽  
Jennifer E Snyder-Cappione ◽  
Samantha E Parker ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Infant Health ◽  
Cytokine Production ◽  
Term Infant ◽  
Late Gestation ◽  
Serum Samples ◽  
Inflammatory Cytokine Production ◽  
Cytokine Assay ◽  
In Pregnancy

Objective: SARS-CoV-2 infection induces significant inflammatory cytokine production in adults, but infant cytokine signatures in pregnancies affected by maternal SARS-CoV-2 are less well characterized. We aimed to evaluate cytokine profiles of mothers and their infants following COVID-19 in pregnancy. Study Design: Serum samples at delivery from 31 mother-infant dyads with maternal SARS-CoV-2 infection in pregnancy (COVID) were examined in comparison to 29 control dyads (Control). Samples were evaluated using a 13-plex cytokine assay. Results: In comparison with controls, interleukin (IL)-6 and interferon gamma-induced protein 10 (IP-10) were higher in COVID maternal and infant samples (p<0.05) and IL-8 uniquely elevated in COVID infant samples (p<0.05). Significant elevations in IL-6, IP-10 and IL-8 were found among both early (1st/2nd Trimester) and late (3rd Trimester) maternal SARS-CoV-2 infections. Conclusions: Maternal SARS-CoV-2 infections throughout gestation are associated with increased maternal and infant inflammatory cytokines at birth with potential to impact long-term infant health.

scholarly journals Blockade of 4-1BB and 4-1BBL Interaction Reduces Obesity-Induced Skeletal Muscle Inflammation

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Ngoc Hoan Le ◽  
Chu-Sook Kim ◽  
Thai Hien Tu ◽  
Hye-Sun Choi ◽  
Byung-Sam Kim ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Inflammatory Cytokines ◽  
High Fat Diet ◽  
Inflammatory Cytokine ◽  
Cytokine Production ◽  
Muscle Cells ◽  
Macrophage Infiltration ◽  
High Fat ◽  
Inflammatory Cytokine Production ◽  
Muscle Inflammation

Obesity-induced skeletal muscle inflammation is characterized by increased macrophage infiltration and inflammatory cytokine production. In this study, we investigated whether 4-1BB, a member of the TNF receptor superfamily (TNFRSF9) that provides inflammatory signals, participates in obesity-induced skeletal muscle inflammation. Expression of the 4-1BB gene, accompanied by increased levels of inflammatory cytokines, was markedly upregulated in the skeletal muscle of obese mice fed a high-fat diet, in muscle cells treated with obesity factors, and in cocultured muscle cells/macrophages. In vitro stimulation of 4-1BB with agonistic antibody increased inflammatory cytokine levels in TNFα-pretreated muscle cells, and this effect was absent in cells derived from 4-1BB-deficient mice. Conversely, disruption of the interaction between 4-1BB and its ligand (4-1BBL) with blocking antibody decreased the release of inflammatory cytokines from cocultured muscle cells/macrophages. Moreover, deficiency of 4-1BB markedly reduced macrophage infiltration and inflammatory cytokine production in the skeletal muscle of mice fed a high-fat diet. These findings indicate that 4-1BB mediates the inflammatory responses in obese skeletal muscle by interacting with its ligand 4-1BBL on macrophages. Therefore, 4-1BB and 4-1BBL may be useful targets for prevention of obesity-induced inflammation in skeletal muscle.

scholarly journals The true cost of in-patient obesity: impact of obesity on inflammatory stress and morbidity

2010 ◽  
Vol 69 (4) ◽  
pp. 511-517 ◽  
Author(s):  
Robert F. Grimble
Keyword(s):  
Inflammatory Cytokines ◽  
Inflammatory Cytokine ◽  
Cytokine Production ◽  
The Body ◽  
Morbidity And Mortality ◽  
Metabolic Effects ◽  
Inflammatory Cytokine Production ◽  
Inflammatory Stress ◽  
Wide Range ◽  
The Impact

The objective of the present review is to provide an overview of the metabolic effects of pro-inflammatory cytokine production during infection and injury; to highlight the disadvantages of pro-inflammatory cytokine production and inflammatory stress on morbidity and mortality of patients; to identify the influence of genetics and adiposity on inflammatory stress in patients and to indicate how nutrients may modulate the inflammatory response in patients. Recent research has shown clearly that adipose tissue actively secretes a wide range of pro- and anti-inflammatory cytokines. Paradoxically, although inflammation is an essential part of the response of the body to infection, surgery and trauma, it can adversely affect patient outcome. The metabolic effects of inflammation are mediated by pro-inflammatory cytokines. Metabolic effects include insulin insensitivity, hyperlipidaemia, muscle protein loss and oxidant stress. These effects, as well as being present during infective disease, are also present in diseases with a covert inflammatory basis. These latter diseases include obesity and type 2 diabetes mellitus. Inflammatory stress also increases during aging. The level of cytokine production, within individuals, is influenced by single nucleotide polymorphisms (SNP) in cytokine genes. The combination of SNP controls the relative level of inflammatory stress in both overt and covert inflammatory diseases. The impact of cytokine genotype on the intensity of inflammatory stress derived from an obese state is unknown. While studies remain to be done in the latter context, evidence shows that these genomic characteristics influence morbidity and mortality in infectious disease and diseases with an underlying inflammatory basis and thereby influence the cost of in-patient obesity. Antioxidants andn-3 PUFA alter the intensity of the inflammatory process. Recent studies show that genotypic factors influence the effectiveness of immunonutrients. A better understanding of this aspect of nutrient–gene interactions and of the genomic factors that influence the intensity of inflammation during disease will help in the more effective targeting of nutritional therapy.

Abstract 205: Ouabain Activates the NF-κB Pathway in Macrophages via Na/K-ATPase/TLR4 Complex Leading to Pro-Inflammatory Cytokine Production

2015 ◽  
Vol 35 (suppl_1) ◽  
Author(s):  
Yiliang Chen ◽  
Roy L Silverstein
Keyword(s):  
Inflammatory Cytokines ◽  
Systemic Inflammation ◽  
Inflammatory Cytokine ◽  
Cytokine Production ◽  
Culture Media ◽  
Mrna Level ◽  
Mrna Levels ◽  
Inflammatory Cytokine Production ◽  
Protein Levels ◽  
Pro Inflammatory Cytokines

Cardiotonic steroids such as ouabain, digoxin, and marinobufagenin are known ligands for the plasma membrane receptor Na/K-ATPase (NKA). These ligands are able to stimulate interaction of the NKA with other membrane and cytosolic proteins leading to cellular events such as activation of kinase cascades and gene transcription. Endogenous cardiotonic steroids have been detected in human circulation and interestingly their levels were elevated in human patients with hypertension, congestive heart failure and diabetes, all of which were associated with chronic systemic inflammation. However, the role of cardiotonic steroids in systemic inflammation and immunity has not been well studied. We previously discovered that ouabain stimulated macrophages to produce pro-inflammatory cytokines, many of which are known targets of the transcription factor, NF-κB. Therefore, we hypothesized that ouabain activates NF-κB pathway leading to pro-inflammatory cytokine production in macrophages. Using Western blot and densitometry analysis, we showed that physiological concentrations of ouabain promoted IκBα degradation (as low as 5 nM ouabain decreased IκBα level by 66.8%±7.4%, n=4). This was accompanied by NF-κB translocation from cytoplasm to the nuclei as shown by immunocytochemistry (% of nuclei NF-κB signals increased from 30.5%±2.3% in control to 62.2%±2.6% in ouabain-treated macrophages, n>25). Moreover, via quantitative RT-PCR (n=3), we found that ouabain increased mRNA levels of pro-inflammatory cytokines such as MCP-1 (3.2±1.1 fold), TNF-α (59.7±35.6 fold), and CXCL-10 (2.8±1.6 fold), all of which are known NF-κB targets. Consistent with the increase in mRNA level, we found that MCP-1 protein levels were elevated in both cell lysates (1.8±0.3 fold) and culture media (1.4±0.1 fold; n=4). Addition of an NF-κB inhibitor blocked MCP-1 production induced by ouabain (n=4). Mechanistically, ouabain stimulated interaction between NKA and TLR4 as shown by Co-Immunoprecipitation (n=3). Blockade of TLR4 signaling using a specific peptide inhibitor, CLI-095, abolished the ouabain effect on NF-κB activation (n=3). We conclude that ouabain activates NF-κB through NKA/TLR4 complex leading to pro-inflammatory cytokine production by macrophages.

scholarly journals Downregulation of Inflammatory Cytokine Release from IL-1β and LPS-Stimulated PBMC Orchestrated by ST2825, a MyD88 Dimerisation Inhibitor

Molecules ◽  
2020 ◽  
Vol 25 (18) ◽  
pp. 4322
Author(s):  
Sergio Ramírez-Pérez ◽  
Luis Alexis Hernández-Palma ◽  
Edith Oregon-Romero ◽  
Brian Uriel Anaya-Macías ◽  
Samuel García-Arellano ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Inflammatory Cytokine ◽  
Mononuclear Cells ◽  
Cytokine Production ◽  
Primary Response ◽  
Peripheral Blood Mononuclear ◽  
Inflammatory Cytokine Production ◽  
Ifn Γ ◽  
Anti Inflammatory ◽  
Pathway Inhibition

The inflammatory process implicates homeostasis disruption and increased production of inflammatory mediators. Myeloid differentiation primary response 88 (MyD88) is an essential protein recruited after lipopolysaccharide (LPS) and interleukin (IL)-1β stimulation, a process that converges in nuclear factor kappa B (NF-κB) activation, as well as a transcription of several genes of both pro- and anti-inflammatory cytokines. The inhibition of MyD88 has shown efficacy by decrease inflammatory response, and has demonstrated potential application as a therapeutic target in chronic diseases. In this study, we investigate the effect of MyD88 dimerisation inhibitor ST2825 on cytokine production from rhIL-1β and LPS-stimulated peripheral blood mononuclear cells (PBMC) from healthy blood donors (HBD). ST2825 significantly downregulates the production of IFN-γ, IL-6, IL-12, IL-2, IL-15, IL-7, VEGF, IL-1Ra, IL-4, IL-5, IL-13 and IL-9 (p < 0.05) in LPS-stimulated PBMC. Moreover, ST2825 had a relatively low impact on IL-1β signalling pathway inhibition, showing that only a few specific cytokines, such as IFN-γ and IL-1Ra, are inhibited in rhIL-1β-stimulated PBMC (p < 0.01). In conclusion, MyD88 dimerisation inhibitor ST2825 showed high efficacy by inhibiting pro- and anti-inflammatory cytokine production in LPS-stimulated PBMC. Moreover, although rhIL-1β induced a sustained cytokine production (p < 0.05), ST2825 did not show a significant effect in the secretion of neither pro- nor anti-inflammatory cytokines in rhIL-1β-stimulated PBMC.

The efficacy and tolerability of combination antiretroviral therapy in pregnancy: infant and maternal outcome

2000 ◽  
Vol 11 (4) ◽  
pp. 220-223 ◽  
Author(s):  
S M Clarke ◽  
F Mulcahy ◽  
C M Healy ◽  
S Condon ◽  
K M Butler
Keyword(s):  
Antiretroviral Therapy ◽  
Management Strategies ◽  
Term Infant ◽  
Hiv Positive ◽  
Plasma Viraemia ◽  
Added Benefit ◽  
Short And Long Term ◽  
The Republic ◽  
In Pregnancy

Antiretroviral therapy (ART) and Caesarean section (CS) delivery significantly reduce the risk of vertically transmitted HIV infection. Attention must focus on determining the optimal management strategy for HIV-positive pregnancies. Guidelines must reflect not only the activity and tolerability of combination ART in pregnancy for mother and infant and the potential short and long-term infant toxicity, but also whether surgical delivery can confer an added benefit if combination ART had reduced plasma viraemia to undetectable levels. To aid the development of management strategies for the Republic of Ireland, a retrospective detailed review of all HIV-positive pregnancies since the introduction of combination ART was undertaken. Since 1997 there have been 25 deliveries to 24 women. Combination ART reduced plasma viraemia to undetectable levels in 76% mothers at delivery. The CS rate was 28% and no unanticipated infant toxicity was encountered. To date no infant has proven infected. Three infants have seroreverted and 24 of 26 infants have had at least 2 negative HIV ribonucleic acid (RNA) and polymerase chain reaction (PCR) tests. Two infants are less than one month old. In this study, the CS rate of 28% is below that reported from many centres yet no vertical transmission was found. Given the efficacy of ART in reducing plasma viraemia, the additional benefit of CS for these women is questionable.

scholarly journals Anti-inflammatory effect of lavender (Lavandula angustifolia Mill.) essential oil prepared during different plant phenophases on THP-1 macrophages

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Edina Pandur ◽  
Alex Balatinácz ◽  
Giuseppe Micalizzi ◽  
Luigi Mondello ◽  
Adrienn Horváth ◽  
...  
Keyword(s):  
Essential Oil ◽  
Essential Oils ◽  
Inflammatory Cytokines ◽  
Inflammatory Cytokine ◽  
Cytokine Production ◽  
Flowering Period ◽  
Inflammatory Cytokine Production ◽  
Beginning Of Flowering ◽  
Anti Inflammatory ◽  
Pro Inflammatory Cytokines

Abstract Background Pseudomonas aeruginosa is the most common Gram-negative bacterium associated with nosocomial respiratory infections. Lavender essential oil is mainly used in aromatherapy, but it has several pharmacological and therapeutic properties. Furthermore, it possesses antifungal and antibacterial activities. The anti-inflammatory activity of essential oils may depend on the composition and the ratio of the compounds. The constitution of the essential oils extracted from the different stages of flowering period varies, which makes it plausible that the collection time of the flowers influences the anti-inflammatory effects. Different types of essential oils reduce inflammation acting similarly by modulating the activity and action of the NFκB signalling pathway, which is the major regulator of the transcription of pro-inflammatory cytokines. Methods Lavender essential oils were distilled from lavender plant cultivated in Hungary and the flowers were harvested at the beginning and at the end of flowering period. The experiments were carried out on THP-1 human monocyte/macrophage cell line as in vitro cell culture model for monitoring the effects of lavender essential oils and the main compound linalool on P. aeruginosa LPS stimulated inflammation. The mRNA and protein levels of four pro-inflammatory cytokines, IL-6, IL-1β, IL-8 and TNFα were determined by Real Time PCR and ELISA measurements. The effects of essential oils were compared to the response to two NFκB inhibitors, luteolin and ACHP. Results Linalool and lavender essential oil extracted from plants at the beginning of flowering period were successful in decreasing pro-inflammatory cytokine production following LPS pretreatment. In case of IL-8 and IL-1β lavender oil showed stronger effect compared to linalool and both of them acted similarly to NFκB inhibitors. Pretreatments with linalool and lavender essential oil/beginning of flowering period prevented pro-inflammatory cytokine production compared to LPS treatment alone. Although lavender essential oil/end of flowering period decreased IL-6, IL-1β and IL-8 mRNA expression in case of LPS pretreatment, it was not capable to reduce cytokine secretion. Conclusion Based on our results it has been proven that lavender essential oil extracted at the beginning of flowering period is a potent inhibitor of the synthesis of four pro-inflammatory cytokines IL-6, IL-8, IL-β and TNFα of THP-1 cells. This supports the relevance of the collection of the lavender flowers from early blooming period for essential oil production and for the utilization as an anti-inflammatory treatment.

scholarly journals Histone deacetylase inhibition reduces deleterious cytokine release induced by ingenol stimulation

2017 ◽  
Author(s):  
Erin T. Larragoite ◽  
Laura J. Martins ◽  
Adam M. Spivak ◽  
Racheal A. Nell ◽  
Vicente Planelles
Keyword(s):  
Histone Deacetylase ◽  
Inflammatory Cytokines ◽  
Inflammatory Cytokine ◽  
Cytokine Production ◽  
Ex Vivo ◽  
Viral Reactivation ◽  
Inflammatory Cytokine Production ◽  
Epigenetic Modifier ◽  
Hiv 1 ◽  
Pro Inflammatory Cytokines

AbstractIntroductionThough antiretroviral therapy has led to viral suppression and increased quality of life for patients living with HIV-1, strategies to eliminate the HIV-1 latent reservoir are still necessary to eliminate HIV. Latency reversal with superior latency reversal agents (LRAs) such as protein kinase C (PKC) agonists is a promising strategy for unveiling and eliminating the latent HIV-1 reservoir. However, PKC agonists induce T cell activation and deleterious pro- inflammatory cytokine production. Secondary pharmacological agents combined with LRAs have been previously shown to reduce deleterious pro-inflammatory cytokine secretion without inhibiting HIV-1 viral reactivation. Histone deacetylase inhibitors (HDACi) are also known for inhibiting deleterious pro-inflammatory cytokines in the context of graft-versus-host disease and rheumatoid arthritis in addition to being known to synergize with PKC agonists. In this study we investigated whether HDACi and other epigenetic modifiers could decrease PKC- induced pro-inflammatory cytokines secretion while simultaneously synergizing with the PKC agonists Ingenol-3,20-dibenzoate, to enhance latency reversal.MethodsWe screened an epigenetic modifier library in health donor human peripheral blood mononuclear cells (PBMCs) to identify compounds (‘hits’) that reduced intracellular IL-6 pro-inflammatory cytokine production induced by PKC agonist Ingenol-3,20-dibenzoate. We then further tested reducers of intracellular IL-6 (‘hits’) for their ability to synergize with Ingenol-3,20-dibenzoate in the J-LAT 10.6 model of HIV-1 latency. The most promising epigenetic modifier from both screens, the HDACi Panobinostat, was then further tested for its ability to reduce pro-inflammatory cytokines and synergize with Ingenol-3,20-dibenzoate.ResultsWe show that co-treatment with Ingenol-3,20-dibenzoate and Panobinostat reduces pro-inflammatory cytokines and enhances latency reversal in vitro. Panobinostat suppressed pro-inflammatory cytokine production when combined with Ingenol-3,20- dibenzoate ex vivo when using aviremic patient cells, but antagonized Ingenol-3,20-dibenzoate dependent latency reversal ex vivo.ConclusionThe combination of Panobinostat and Ingenol-3,20-dibenzoate reduces deleterious cytokine production but is not a suitable latency reversal combination therapy.

scholarly journals Kaposi's Sarcoma-Associated Herpesvirus OX2 Glycoprotein Activates Myeloid-Lineage Cells To Induce Inflammatory Cytokine Production

2002 ◽  
Vol 76 (10) ◽  
pp. 4688-4698 ◽  
Author(s):  
Young-Hwa Chung ◽  
Robert E. Means ◽  
Joong-Kook Choi ◽  
Bok-Soo Lee ◽  
Jae U. Jung
Keyword(s):  
Inflammatory Cytokines ◽  
Kaposi's Sarcoma ◽  
Inflammatory Cytokine ◽  
Cytokine Production ◽  
Kaposi’S Sarcoma ◽  
Myeloid Lineage ◽  
Inflammatory Cytokine Production ◽  
Monocyte Chemoattractant Protein 1 ◽  
Kaposi's Sarcoma Associated Herpesvirus ◽  
Kaposi’S Sarcoma Associated Herpesvirus

ABSTRACT Kaposi's sarcoma is an inflammatory cytokine-mediated angioproliferative disease which is triggered by infection by Kaposi's sarcoma-associated herpesvirus (KSHV). KSHV contains an open reading frame, K14, that has significant homology with cellular OX2, designated viral OX2 (vOX2). In this report, we demonstrate that vOX2 encodes a glycosylated cell surface protein with an apparent molecular mass of 55 kDa. Purified glycosylated vOX2 protein dramatically stimulated primary monocytes, macrophages, and dendritic cells to produce the inflammatory cytokines interleukin 1β (IL-1β), IL-6, monocyte chemoattractant protein 1, and TNF-α. Furthermore, expression of vOX2 on B lymphocytes stimulated monocytes to produce inflammatory cytokines in mixed culture. These results demonstrate that like its cellular counterpart, vOX2 targets myeloid-lineage cells, but unlike cellular OX2, which delivers a restrictive signal, KSHV vOX2 provides an activating signal, resulting in the production of inflammatory cytokines. Thus, this is a novel viral strategy where KSHV has acquired the cellular OX2 gene to induce inflammatory cytokine production, which potentially promotes the cytokine-mediated angiogenic proliferation of KSHV-infected cells.

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