Anti-inflammatory properties of pro-inflammatory interferon-gamma.

https://www.cell.com/trends/immunology/pdf/S1471-4906(08)00198-1.pdf

How interferon-γ keeps autoimmune diseases in check

IL-18 and IL-18 binding protein (IL-18BP) are two newly described opponents in the cytokine network. Local concentrations of these two players may determine biological functions of IL-18 in the context of inflammation, infection, and cancer. As IL-18 appears to be involved in the pathogenesis of Crohn’s disease and may modulate tumor growth, we investigated the IL-18/IL-18BPa system in the human colon carcinoma/epithelial cell line DLD-1. In this study, we report that IFN-γ induces expression and release of IL-18BPa from DLD-1 cells. mRNA induction and secretion of IL-18BPa immunoreactivity were associated with an activity that significantly impaired release of IFN-γ by IL-12/IL-18-stimulated PBMC. Inducibility of IL-18BPa by IFN-γ was also observed in LoVo, Caco-2, and HCT116 human colon carcinoma cell lines and in the human keratinocyte cell line HaCaT. Induction of IL-18BPa in colon carcinoma/epithelial cell lines was suppressed by coincubation with sodium butyrate. IFN-γ-mediated IL-18BPa and its suppression by sodium butyrate were confirmed in organ cultures of intestinal colonic biopsy specimens. In contrast, sodium butyrate did not modulate expression of IL-18. The present data suggest that IFN-γ may limit biological functions of IL-18 at sites of colonic immune activation by inducing IL-18BPa production. Down-regulation of IL-18BPa by sodium butyrate suggests that reinforcement of local IL-18 activity may contribute to actions of this short-chain fatty acid in the colonic microenvironment.

Expression and Release of IL-18 Binding Protein in Response to IFN-γ

Summary Background Hydroxychloroquine, a drug commonly used in the treatment of rheumatoid arthritis, has received much negative publicity for adverse events associated with its authorisation for emergency use to treat patients with COVID-19 pneumonia. We studied the safety of hydroxychloroquine, alone and in combination with azithromycin, to determine the risk associated with its use in routine care in patients with rheumatoid arthritis. Methods In this multinational, retrospective study, new user cohort studies in patients with rheumatoid arthritis aged 18 years or older and initiating hydroxychloroquine were compared with those initiating sulfasalazine and followed up over 30 days, with 16 severe adverse events studied. Self-controlled case series were done to further establish safety in wider populations, and included all users of hydroxychloroquine regardless of rheumatoid arthritis status or indication. Separately, severe adverse events associated with hydroxychloroquine plus azithromycin (compared with hydroxychloroquine plus amoxicillin) were studied. Data comprised 14 sources of claims data or electronic medical records from Germany, Japan, the Netherlands, Spain, the UK, and the USA. Propensity score stratification and calibration using negative control outcomes were used to address confounding. Cox models were fitted to estimate calibrated hazard ratios (HRs) according to drug use. Estimates were pooled where the I2 value was less than 0·4. Findings The study included 956 374 users of hydroxychloroquine, 310 350 users of sulfasalazine, 323 122 users of hydroxychloroquine plus azithromycin, and 351 956 users of hydroxychloroquine plus amoxicillin. No excess risk of severe adverse events was identified when 30-day hydroxychloroquine and sulfasalazine use were compared. Self-controlled case series confirmed these findings. However, long-term use of hydroxychloroquine appeared to be associated with increased cardiovascular mortality (calibrated HR 1·65 [95% CI 1·12–2·44]). Addition of azithromycin appeared to be associated with an increased risk of 30-day cardiovascular mortality (calibrated HR 2·19 [95% CI 1·22–3·95]), chest pain or angina (1·15 [1·05–1·26]), and heart failure (1·22 [1·02–1·45]). Interpretation Hydroxychloroquine treatment appears to have no increased risk in the short term among patients with rheumatoid arthritis, but in the long term it appears to be associated with excess cardiovascular mortality. The addition of azithromycin increases the risk of heart failure and cardiovascular mortality even in the short term. We call for careful consideration of the benefit–risk trade-off when counselling those on hydroxychloroquine treatment. Funding National Institute for Health Research (NIHR) Oxford Biomedical Research Centre, NIHR Senior Research Fellowship programme, US National Institutes of Health, US Department of Veterans Affairs, Janssen Research and Development, IQVIA, Korea Health Industry Development Institute through the Ministry of Health and Welfare Republic of Korea, Versus Arthritis, UK Medical Research Council Doctoral Training Partnership, Foundation Alfonso Martin Escudero, Innovation Fund Denmark, Novo Nordisk Foundation, Singapore Ministry of Health's National Medical Research Council Open Fund Large Collaborative Grant, VINCI, Innovative Medicines Initiative 2 Joint Undertaking, EU's Horizon 2020 research and innovation programme, and European Federation of Pharmaceutical Industries and Associations.

/pdf/risk-of-hydroxychloroquine-alone-and-in-combination-with-253naghdqh.pdf

Risk of hydroxychloroquine alone and in combination with azithromycin in the treatment of rheumatoid arthritis: a multinational, retrospective study.

Osteoimmunology is the interdiscipline that focuses on the relationship between the skeletal and immune systems. They are interconnected by shared signal pathways and cytokines. Interferon-gamma (IFN-γ) plays important roles in immune responses and bone metabolism. IFN-γ enhances macrophage activation and antigen presentation. It regulates antiviral and antibacterial immunity as well as signal transduction. IFN-γ can promote osteoblast differentiation and inhibit bone marrow adipocyte formation. IFN-γ plays dual role in osteoclasts depending on its stage. Furthermore, IFN-γ is an important pathogenetic factor in some immune-mediated bone diseases including rheumatoid arthritis, postmenopausal osteoporosis, and acquired immunodeficiency syndrome. This review will discuss the contradictory findings of IFN-γ in osteoimmunology and its clinical application potential.

/pdf/interferon-gamma-mediated-osteoimmunology-1n35msrd10.pdf

Interferon-Gamma-Mediated Osteoimmunology.

The controlled clinical trial reported here is part of a multicenter clinical and basic research project, sponsored by the German Federal Minister of Science and Technology, directed by a standing commission of the president of the Max-Planck-Gesellschaft, and coordinated by the Max-Planck-Institut fur Biochemie, Munchen. Overall, 249 patients with rheumatoid arthritis (RA) were enrolled by 16 participating hospitals. In addition to NSAID treatment, patients were randomly given either interferon gamma (IFN-γ) or placebo. In the IFN-γ group, 107 patients were evaluated and in the control group, 116 patients were evaluated. The response rate after 3 months of treatment, according to joint pain indexes, was significantly higher in the IFN-γ group with an error probability of 1%. IFN-γ was able to reduce the quantity of corticosteroids administered. Compared with the control group, the IFN-γ group benefited considering all parameters measured. Most important side effects were transient fever and transient influenza-like symptoms; all other adverse events were comparable in both groups.

Double blind controlled phase III multicenter clinical trial with interferon gamma in rheumatoid arthritis

The post COVID-19 syndrome (PCS) is an emerging phenomenon worldwide with enormous socioeconomic impact. While many patients describe neuropsychiatric deficits, the symptoms are yet to be assessed and defined systematically. In this prospective cohort study, we report on the results of a neuropsychiatric consultation implemented in May 2021. A cohort of 105 consecutive patients with merely mild acute course of disease was identified by its high symptom load 6 months post infection using a standardized neurocognitive and psychiatric-psychosomatic assessment. In this cohort, we found a strong correlation between higher scores in questionnaires for fatigue (MFI-20), somatization (PHQ15) and depression (PHQ9) and worse functional outcome as measured by the post COVID functional scale (PCFS). In contrast, neurocognitive scales correlated with age, but not with PCFS. Standard laboratory and cardiopulmonary biomarkers did not differ between the group of patients with predominant neuropsychiatric symptoms and a control group of neuropsychiatrically unaffected PCS patients. Our study delineates a phenotype of PCS dominated by symptoms of fatigue, somatisation and depression. The strong association of psychiatric and psychosomatic symptoms with the PCFS warrants a systematic evaluation of psychosocial side effects of the pandemic itself and psychiatric comorbidities on the long-term outcome of patients with SARS-CoV-2 infection.

/pdf/neuropsychiatric-phenotype-of-post-covid-19-syndrome-in-non-3a4733bw.pdf

Neuropsychiatric phenotype of post COVID-19 syndrome in non-hospitalized patients

Abstract: This study introduces a 3-week group program designed for patients with neurocognitive post-COVID-19 syndrome (PCS). The program represents a combination of evidence-based components of neurorehabilitation and cognitive behavioral therapy (CBT). Following a detailed assessment, we develop a personalized bio-psycho-social model that integrates perceived complaints and identifies modifiable and influencing factors. We employed physiotherapeutic, cognitive, and communicative training methods to improve patients’ awareness of energy limits and implement compensatory strategies, including pacing and mindfulness techniques. N = 33 patients completed the program between June 2021 and November 2022. A pre-post comparison of questionnaire-based self-assessments revealed significant positive effects on mood, self-efficacy, and participation but not on fatigue symptoms. The study provides recommendations for the neuropsychological treatment of patients with PCS.

The Leipzig Treatment Program for Interdisciplinary Diagnosis and Therapy of Neurocognitive Post-COVID Symptoms

Handle everyday research tasks with reliable, citation-backed results

Your personal Research Agent to handle research tasks with citation-backed results

Popular Tasks used by Researchers

How can I help with your research?

Meet SciSpace

Get more enhanced response by uploading the PDFs you want me to reference.

No relevant PDFs in your library

SciSpace is the AI research assistant for academics. Run systematic literature reviews on 280M+ papers, and write papers with cited sources. Trusted by 1M+ students, PhDs & researchers.

SciSpace | AI for Research

Analyze PDFs

Code & Manuscripts

Funding & Grants

Literature & Patents

Medical & Clinical Data

Systematic Review

Visualize & Present

Web & Data

Build a Google Scholar-like website for your research.

Build a website

Create charts and images for your research

Create a Chart

Write a paper for submission to a journal

Draft a manuscript

Patent Search

Design eye-catching scientific posters in minutes.

Scientific Poster Generation

Systematic Literature Review

One task is running at the moment. Your messages will be shown right after.

Drag and drop or click here to browse

Loved by <highlight>1 million+</highlight> researchers

Extract a list of specific topics and their sources from unstructured text

Topics

Compare and analyze relevant papers that matches with your search

Papers

Get insights from PDFs and bookmarked papers from your library

My library

Recent searches

Try searching for:

Catch AI-generated content in scholarly and non-scholarly content

{ai} Detector

Ai Writer

Get PDF Summaries, highlighted text explanations 

Chat with PDF

Effortlessly create in-text citations and bibliographies in APA and 2,500 other formats

Citation generator

Get explanations, summaries, and answers on academic papers

Ease up your research workflow with {scispace}'s cohort of exciting AI tools

Elevate your academic writing skills and convey your ideas the way you want

Paraphraser

Explore our range of reading and writing tools

Your file is being prepared and should be ready in a few minutes. If it's a large file, it might take a bit longer. You can close this window, and we'll email you the file when it's done.

You have reached a maximum limit of <strong>{limit}</strong> columns in the table. Remove at least <strong>1</strong> column to add or create another one.

S. Herzig

Author Tools

Chat about Author

Papers

Double blind controlled phase III multicenter clinical trial with interferon gamma in rheumatoid arthritis

Neuropsychiatric phenotype of post COVID-19 syndrome in non-hospitalized patients

The Leipzig Treatment Program for Interdisciplinary Diagnosis and Therapy of Neurocognitive Post-COVID Symptoms