Immunotherapy in psoriasis

Immunotherapy ◽  
2021 ◽  
Author(s):  
Lilla Landeck ◽  
Robert Sabat ◽  
Kamran Ghoreschi ◽  
Xiao-Yong Man ◽  
Katja Fuhrmeister ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Soluble Receptor ◽  
Cytokine Network ◽  
The Past ◽  
Modes Of Action ◽  
Tnf Α ◽  
The Right ◽  
Human Cytokine ◽  
Huge Progress

Over the past two decades, a huge progress in the treatment of psoriasis was achieved by targeting the human cytokine network. At present, 11 biologicals – antibodies, and a soluble receptor – are used to neutralize key inflammatory cytokines. Based on their targets, they can be grouped into the following four classes: TNF-α-, IL-12/23-, IL-17- and IL-23-inhibitors. The number of substances, but also the different modes of action may be challenging, when selecting the right drug for an individual patient. In this article, we provide an overview of the available biologicals in the treatment of psoriasis, including their advantages and limitations, and summarize criteria for therapy selection.

scholarly journals Cytokines in the blood of patients with type 2 diabetes mellitus depending on the level of overweight/obesity (literature review and own data)

2021 ◽  
Vol 17 (7) ◽  
pp. 534-551
Author(s):  
K.P. Zak ◽  
V.V. Popova ◽  
V.L. Orlenko ◽  
O.V. Furmanova ◽  
N.D. Tronko
Keyword(s):  
Type 2 Diabetes ◽  
Inflammatory Cytokines ◽  
Proinflammatory Cytokines ◽  
Peripheral Blood ◽  
Control Group ◽  
Obese Women ◽  
Cytokine Network ◽  
Tnf Α ◽  
Anti Inflammatory

The paper analyzes the current literature data and the results of our own researches concerning the state of the cytokine network: pro- and anti-inflammatory cytokines (interleukin (IL) 1α, IL-1β, IL-4, IL-6, IL-10, IL-17 and tumor necrosis factor (TNF) α), α- and β-chemokines, including IL-8 and IL-16, as well as adipokines (leptin and adiponectin) in the peripheral blood of patients with type 2 diabetes (T2D) with normal and increased body weight/obesity. It has been shown that patients with T2D are cha­racterized by an increased content of proinflammatory cytokines (IL-1, IL-6, IL-17, TNFα), α- and β-chemokines in the peripheral blood, including IL-8 and IL-16, as well as leptin with a decrease in adiponectin content. In lean patients (with body mass index (BMI) < 25.5 kg/m2) compared to lean normoglycemic individuals from the control group (BMI < 25.5 kg/m2), there is a small but significant increase in IL-1β, IL-6, IL-17, TNFα and leptin, which, as BMI increases, significantly increases in severe obesity (BMI > 30.0 kg/m2), especially in obese women (BMI > 35.0 kg/m2). Similarly, an increase in proinflammatory cytokines is observed in normoglycemic people, but not as signifi­cant as in T2D. Less clear data were obtained when during determination of the anti-inflammatory cytokines IL-4 and IL-10, which is explained by a significant polymorphism of their genes, and both protective and compensatory effects on pro-inflammatory cytokine rise. In T2D patients, especially those with obesity, there is an increase in the leptin level and a decrease in the adiponectin content. The severity of the course and the percentage of mortality are closely associated with the BMI of patients. The effectiveness of the fight against an increase in the incidence of T2D should be primarily aimed at preventing obesity, and in case of already developed T2D — at reducing concomitant obesity. The analysis of the data presented also suggests that a sharp increase in the content of pro-inflammatory cytokines (so called cytokine storm) observed in patients with T2D and obesity infected with COVID-19, is a consequence of the summation and potentiation of already existing inflammatory process.

scholarly journals Association between resting-state functional connectivity of amygdala subregions and peripheral pro-inflammation cytokines levels in bipolar disorder

2020 ◽  
Author(s):  
Jiaying Gong ◽  
Guanmao Chen ◽  
Feng Chen ◽  
Shuming Zhong ◽  
Pan Chen ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
Functional Connectivity ◽  
Inflammatory Cytokines ◽  
Negative Correlation ◽  
Resting State ◽  
Immune Dysregulation ◽  
Medial Amygdala ◽  
Tnf Α ◽  
The Right ◽  
Pro Inflammatory Cytokines

Abstract Background: The pathophysiological mechanisms of mood disorders including bipolar disorder (BD) are not completely known, and systemic inflammation and immune dysregulation are considered as risk factors of it. Previous neuroimaging studies have proved metabolic, structural and functional abnormalities of the amygdala in BD patients, suggesting the vital role of amygdala in BD patients. This study aimed to test the underlying neural mechanism of inflammation-induced functional connectivity (FC) in the amygdala subregions of BD patients.Methods: Resting-state functional MRI (rs-fMRI) was used to delineate the amygdala FC from two pairs of amygdala seed regions (the bilateral lateral and medial amygdala) in 51 unmedicated BD patients and 69 healthy controls (HCs). The levels of pro-inflammatory cytokines including interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α were measured in the serum. The correlation between abnormal levels of pro-inflammatory cytokines and FC values were calculated in BD patients.Results: The BD group exhibited decreased FC between the right medial amygdala and bilateral medial frontal cortex (MFC), and decreased FC between the left medial amygdala and the left temporal pole (TP), right orbital inferior frontal gyrus compared with HCs. The BD patients had higher levels of TNF-α than HCs. Correlation analysis showed negative correlation between the TNF-α level and abnormal FC of the right medial amygdala-bilateral MFC; and negative correlation between TNF-α levels and abnormal FC of the left medial amygdala-left TP in BD group.Conclusions: These findings suggest that dysfunctional and immune dysregulation between the amygdala and the frontotemporal circuitry might play a critical role in the pathogenesis of BD.

Inhibition of Pro-Inflammatory Cytokine Secretion by Select Antioxidants in Human Coronary Artery Endothelial Cells

2020 ◽  
Vol 90 (1-2) ◽  
pp. 103-112 ◽  
Author(s):  
Michael J. Haas ◽  
Marilu Jurado-Flores ◽  
Ramadan Hammoud ◽  
Victoria Feng ◽  
Krista Gonzales ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Ascorbic Acid ◽  
Coronary Artery ◽  
Inflammatory Cytokines ◽  
Inflammatory Cytokine ◽  
Culture Media ◽  
Cytokine Secretion ◽  
Human Coronary Artery ◽  
Tnf Α ◽  
Pro Inflammatory Cytokines

Abstract. Inflammatory and oxidative stress in endothelial cells are implicated in the pathogenesis of premature atherosclerosis in diabetes. To determine whether high-dextrose concentrations induce the expression of pro-inflammatory cytokines, human coronary artery endothelial cells (HCAEC) were exposed to either 5.5 or 27.5 mM dextrose for 24-hours and interleukin-1β (IL-1β), interleukin-2 (IL-2), interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor α (TNF α) levels were measured by enzyme immunoassays. To determine the effect of antioxidants on inflammatory cytokine secretion, cells were also treated with α-tocopherol, ascorbic acid, and the glutathione peroxidase mimetic ebselen. Only the concentration of IL-1β in culture media from cells exposed to 27.5 mM dextrose increased relative to cells maintained in 5.5 mM dextrose. Treatment with α-tocopherol (10, 100, and 1,000 μM) and ascorbic acid (15, 150, and 1,500 μM) at the same time that the dextrose was added reduced IL-1β, IL-6, and IL-8 levels in culture media from cells maintained at 5.5 mM dextrose but had no effect on IL-1β, IL-6, and IL-8 levels in cells exposed to 27.5 mM dextrose. However, ebselen treatment reduced IL-1β, IL-6, and IL-8 levels in cells maintained in either 5.5 or 27.5 mM dextrose. IL-2 and TNF α concentrations in culture media were below the limit of detection under all experimental conditions studied suggesting that these cells may not synthesize detectable quantities of these cytokines. These results suggest that dextrose at certain concentrations may increase IL-1β levels and that antioxidants have differential effects on suppressing the secretion of pro-inflammatory cytokines in HCAEC.

COMMONWEALTH Forum: The Politics of Science or the Science of Politics

Commonwealth ◽  
2017 ◽  
Vol 19 (1) ◽  
Author(s):  
John Arway
Keyword(s):  
Public Policy ◽  
Natural Resource ◽  
Factual Information ◽  
The Past ◽  
Difference Of Opinion ◽  
History Of ◽  
The Right ◽  
Scientific Facts ◽  
Environmental Agency ◽  
Laws And Regulations

The challenges of including factual information in public policy and political discussions are many. The difficulties of including scientific facts in these debates can often be frustrating for scientists, politicians and policymakers alike. At times it seems that discussions involve different languages or dialects such that it becomes a challenge to even understand one another’s position. Oftentimes difference of opinion leads to laws and regulations that are tilted to the left or the right. The collaborative balancing to insure public and natural resource interests are protected ends up being accomplished through extensive litigation in the courts. In this article, the author discusses the history of environmental balancing during the past three decades from the perspective of a field biologist who has used the strength of our policies, laws and regulations to fight for the protection of our Commonwealth’s aquatic resources. For the past 7 years, the author has taken over the reins of “the most powerful environmental agency in Pennsylvania” and charted a course using science to properly represent natural resource interests in public policy and political deliberations.

Accelerating Agricultural Growth—Is Irrigation Institutional Reform Necessary? (Distinguishedl Lecture)

1996 ◽  
Vol 35 (4I) ◽  
pp. 399-417 ◽  
Author(s):  
John W. Mellor
Keyword(s):  
Growth Rates ◽  
Irrigation System ◽  
Institutional Reform ◽  
Residual Effect ◽  
Agricultural Growth ◽  
The Past ◽  
Major Reform ◽  
History Of ◽  
The Right ◽  
Economic Growth Rates

The right to the flow of income from water is vigorously pursued, protected, and fought over in any arid part of the world. Pakistan is of course no exception. Reform of irrigation institutions necessarily changes the rights to water, whether it be those of farmers, government, or government functionaries. Those perceived rights may be explicit and broadly accepted, or simply takings that are not even considered legitimate. Nevertheless they will be fought over. Pakistan has a long history of proposals for irrigation reform, little or none being implemented, except as isolated pilot projects. Thus, to propose major changes in irrigation institutions must be clearly shown to have major benefits to justify the hard battles that must be fought and the goodwill of those who might win those battles for reform. Proponents of irrigation institution reform have always argued the necessity of the reforms and the large gains to be achieved. Perhaps, however, those arguments have not been convincing. This paper will briefly outline the failed attempts at irrigation reform to provide an element of reality to the discussion. It will then proceed to make the case of the urgency of reform in a somewhat different manner to the past. Finally, current major reform proposals will be presented. This paper approaches justification of irrigation reform by focusing on the agricultural growth rate. It does so because that is the critical variable influencing poverty rates and is a significant determinant of over-all economic growth rates. The paper decomposes growth rates and suggests a residual effect of deterioration of the irrigation system that is large and calls for policy and institutional reform. The data are notional, suggesting the usefulness of the approach and paves the way for more detailed empirical analysis and enquiry for the future.

Evaluating the efficacy of intra-articular injections of platelet rich plasma (PRP) in rheumatoid arthritis patients and its impact on inflammatory cytokines, disease activity and quality of life.

2020 ◽  
Vol 16 ◽  
Author(s):  
Dalia S. Saif ◽  
Nagwa N. Hegazy ◽  
Enas S. Zahran
Keyword(s):  
Quality Of Life ◽  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Inflammatory Cytokines ◽  
Platelet Rich Plasma ◽  
Joint Inflammation ◽  
Monthly Interval ◽  
Post Injection ◽  
Tnf Α

Background: Among rheumatoid arthritis patients (RA), general disease activity is well regulated by diseasemodifying anti-rheumatic medications (DMARDS), but sometimes local inflammation still persists among a few joints. Adjuvant modern molecular interventions as Platelet Rich Plasma (PRP) with a suggested down regulating effect on inflammatory mediators has a proven effect in management of RA. We aim to evaluate the therapeutic effect of intra-articular PRP versus steroid in RA patients and their impact on inflammatory cytokines IL1B , TNF α, local joint inflammation, disease activity and quality of life (QL). Methods: Open labeled parallel randomized control clinical trial was carried out on 60 RA patients randomly divided into 2 groups, Group 1: included 30 patients received 3 intra-articular injections of PRP at monthly interval, Group 2: included 30 patients received single intra-articular injection of steroid. They were subjected to clinical, laboratory, serum IL1B and TNF α assessment at baseline and at 3, 6 months post injection. Results: Patients of both groups showed improvements in their scores of evaluating tools at 3months post injection and this improvement was persistent in the PRP group up to 6 months post injection while it was continued only for 3 months in the steroid group. Conclusions: PRP is a safe, effective and useful therapy in treating RA patients who had insufficient response and persistent pain and inflammation in just one or two joints through its down regulating effect on inflammatory cytokines IL1B, TNF α with subsequent improvement of local joint inflammation, disease activity and QL.

AAnti-Inflammatory Effects of Plasma Circulating Exosomes Obtained from Normal-Weight and Obese Subjects on Hepatocytes

2020 ◽  
Vol 20 ◽  
Author(s):  
Reza Afrisham ◽  
Sahar Sadegh-Nejadi ◽  
Reza Meshkani ◽  
Solaleh Emamgholipour ◽  
Molood Bagherieh ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Hepg2 Cells ◽  
Human Liver ◽  
Liver Cells ◽  
Normal Weight ◽  
Protein Levels ◽  
Human Liver Cells ◽  
Tnf Α ◽  
Anti Inflammatory

Introduction: Obesity is a disorder with low-grade chronic inflammation that plays a key role in the hepatic inflammation and steatosis. Moreover, there are studies to support the role of exosomes in the cellular communications, the regulation of metabolic homeostasis and immunomodulatory activity. Accordingly, we aimed to evaluate the influence of plasma circulating exosomes derived from females with normal-weight and obesity on the secretion of inflammatory cytokines in human liver cells. Methods: Plasma circulating exosomes were isolated from four normal (N-Exo) and four obese (O-Exo) women. The exosomes were characterized and approved for CD63 expression (common exosomal protein marker) and morphology/size using the western blot and TEM methods, respectively. The exosomes were used for stimulation of HepG2 cells in vitro. After 24 h incubation, the protein levels of TNF-α,IL-6, and IL-1β were measured in the culture supernatant of HepG2 cells using the ELISA kit. Results: The protein levels of IL-6 and TNF-α in the cells treated with O-Exo and N-Exo reduced significantly in comparison with control group (P=0.039 and P<0.001 respectively), while significance differences were not found between normal and obese groups (P=0.808, and P=0.978 respectively). However, no significant differences were found between three groups in term of IL-1β levels (P=0.069). Based on the correlation analysis, the protein levels of IL-6 were positively correlated with TNF-α (r 0.978, P<0.001). Conclusion: These findings suggest that plasma circulating exosomes have probably anti-inflammatory properties independently from body mass index and may decrease the secretion of inflammatory cytokines in liver. However, further investigations in vitro and in vivo are needed to address the anti-inflammatory function of N-Exo and O-Exo in human liver cells and/or other cells.

scholarly journals Punicalagin Prevents Inflammation in LPS-Induced RAW264.7 Macrophages by Inhibiting FoxO3a/Autophagy Signaling Pathway

Nutrients ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 2794 ◽  
Author(s):  
Cao ◽  
Chen ◽  
Ren ◽  
Zhang ◽  
Tan ◽  
...  
Keyword(s):  
Western Blot ◽  
Signaling Pathway ◽  
Inflammatory Cytokines ◽  
Blot Analysis ◽  
Western Blot Analysis ◽  
Inflammatory Responses ◽  
Raw264.7 Macrophages ◽  
Tnf Α ◽  
Autophagy Inhibition ◽  
Pro Inflammatory Cytokines

Punicalagin, a hydrolysable tannin of pomegranate juice, exhibits multiple biological effects, including inhibiting production of pro-inflammatory cytokines in macrophages. Autophagy, an intracellular self-digestion process, has been recently shown to regulate inflammatory responses. In this study, we investigated the anti-inflammatory potential of punicalagin in lipopolysaccharide (LPS) induced RAW264.7 macrophages and uncovered the underlying mechanisms. Punicalagin significantly attenuated, in a concentration-dependent manner, LPS-induced release of NO and decreased pro-inflammatory cytokines TNF-α and IL-6 release at the highest concentration. We found that punicalagin inhibited NF-κB and MAPK activation in LPS-induced RAW264.7 macrophages. Western blot analysis revealed that punicalagin pre-treatment enhanced LC3II, p62 expression, and decreased Beclin1 expression in LPS-induced macrophages. MDC assays were used to determine the autophagic process and the results worked in concert with Western blot analysis. In addition, our observations indicated that LPS-induced releases of NO, TNF-α, and IL-6 were attenuated by treatment with autophagy inhibitor chloroquine, suggesting that autophagy inhibition participated in anti-inflammatory effect. We also found that punicalagin downregulated FoxO3a expression, resulting in autophagy inhibition. Overall these results suggested that punicalagin played an important role in the attenuation of LPS-induced inflammatory responses in RAW264.7 macrophages and that the mechanisms involved downregulation of the FoxO3a/autophagy signaling pathway.

Does the Injunction Gap Violate Implementers’ Fair Trial Rights Under the ECHR?

2020 ◽  
Author(s):  
Léon E Dijkman
Keyword(s):  
Human Rights ◽  
Case Law ◽  
Fair Trial ◽  
European Convention ◽  
The Past ◽  
European Court ◽  
The Subject ◽  
The Right ◽  
Federal Supreme ◽  
Validity Of A Patent

Abstract Germany is one of few jurisdictions with a bifurcated patent system, under which infringement and validity of a patent are established in separate proceedings. Because validity proceedings normally take longer to conclude, it can occur that remedies for infringement are imposed before a decision on the patent’s validity is available. This phenomenon is colloquially known as the ‘injunction gap’ and has been the subject of increasing criticism over the past years. In this article, I examine the injunction gap from the perspective of the right to a fair trial enshrined in Art. 6 of the European Convention on Human Rights. I find that the case law of the European Court of Human Rights interpreting this provision supports criticism of the injunction gap, because imposing infringement remedies with potentially far-reaching consequences before the validity of a patent has been established by a court of law arguably violates defendants’ right to be heard. Such reliance on the patent office’s grant decision is no longer warranted in the light of contemporary invalidation rates. I conclude that the proliferation of the injunction gap should be curbed by an approach to a stay of proceedings which is in line with the test for stays as formulated by Germany’s Federal Supreme Court. Under this test, courts should stay infringement proceedings until the Federal Patent Court or the EPO’s Board of Appeal have ruled on the validity of a patent whenever it is more likely than not that it will be invalidated.

scholarly journals Modulation of ACE-2 mRNA by inflammatory cytokines in human thyroid cells: a pilot study

Endocrine ◽  
2021 ◽  
Author(s):  
Francesca Coperchini ◽  
Gianluca Ricci ◽  
Laura Croce ◽  
Marco Denegri ◽  
Rubina Ruggiero ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Combination Treatment ◽  
Primary Cultures ◽  
Human Thyroid ◽  
Thyroid Cell ◽  
Mrna Levels ◽  
Thyroid Cells ◽  
Tnf Α ◽  
Ifn Γ ◽  
Pro Inflammatory Cytokines

Abstract Introduction Angiotensin-converting-enzyme-2 (ACE-2) was demonstrated to be the receptor for cellular entry of SARS-CoV-2. ACE-2 mRNA was identified in several human tissues and recently also in thyroid cells in vitro. Purpose Aim of the present study was to investigate the effect of pro-inflammatory cytokines on the ACE-2 mRNA levels in human thyroid cells in primary cultures. Methods Primary thyroid cell cultures were treated with IFN-γ and TNF-α alone or in combination for 24 h. ACE-2 mRNA levels were measured by RT-PCR. As a control, the levels of IFN-γ inducible chemokine (CXCL10) were measured in the respective cell culture supernatants. Results The mean levels of ACE-2 mRNA increased after treatment with IFN-γ and TNF-α in all the thyroid cell preparations, while the combination treatment did not consistently synergically increase ACE-2-mRNA. At difference, CXCL10 was consistently increased by IFN-γ and synergically further increased by the combination treatment with IFN-γ + TNF-α, with respect to IFN-γ alone. Conclusions The results of the present study show that IFN-γ and, to a lesser extent TNF-α consistently increase ACE-2 mRNA levels in NHT primary cultures. More interestingly, the combined stimulation (proven to be effective according to the synergic effect registered for CXCL10) produces different responses in terms of ACE-2 mRNA modulation. These results would suggest that elevated levels of pro-inflammatory cytokines could facilitate the entering of the virus in cells by further increasing ACE-2 expression and/or account for the different degree of severity of SARS-COV-2 infection. This hypothesis deserves to be confirmed by further specific studies.

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