Anti-Inflammatory Drugs

2006 ◽  
Author(s):  
Jie Jack Li
Keyword(s):  
Rheumatoid Arthritis ◽  
Inflammatory Diseases ◽  
Heart Diseases ◽  
Chronic Inflammatory Disease ◽  
Medical Society ◽  
Loss Of Function ◽  
Hard Time ◽  
Back Door ◽  
Inflammatory Bowel ◽  
William Osler

Inflammation and immunity, like all other normal reactions of the body, are meant to preserve or restore health. They can nonetheless cause a range of uncomfortable symptoms. Inflammation is such a complicated process that one would have a hard time reaching a consensus on its definition. Historically, inflammation was one of the earliest recognized and defined diseases. Two thousand years ago, Roman physician and encyclopedist Aulus Cornelius Celsus (25 B.C.–50 A.D., not to be confused with Celsius, the unit for temperature) described the four cardinal signs of inflammation: calor (warmth), dolor (pain), tumor (swelling), and rubor (redness). The fifth element of inflammation, functio laesi (loss of function or movement), was noted later. Classic inflammatory diseases include rheumatoid arthritis and Crohn’s disease, an inflammatory bowel disease. However, evidence is mounting that inflammation is implicated in many diseases that are not normally considered inflammatory. For instance, when arterial plaques become inflamed they can burst open, prompting a myriad of heart diseases. Inflammatory bowel conditions greatly increase the risk of colon tumors. Even diabetes has been associated with a number of inflammatory compounds. It was hard to define what inflammation was, but finding a remedy was even more challenging. Aspirin, available in 1880, represented possibly the first really effective treatment for inflammation, whereas cortisone and other corticosteroids were not available for the treatment of rheumatoid arthritis until the early 1950s. Louis Pasteur stated, “Dans les champs de l’observation, le hazard ne favorise que les esprit préparés” [In the field of experimentation, chance favors the prepared mind]. Like numerous cases in drug discovery, Philip S. Hench’s discovery of cortisone for the treatment of rheumatoid arthritis illustrates Pasteur’s point. Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by pain, swelling, and subsequent destruction of joints. Until the late 1940s, there was no viable treatment, and, understandably, pessimism prevailed in medical society about its prognosis. Even William Osler, one of the greatest physicians, said “When an arthritic patient walks in the front door, I want to run out the back door!” The situation did not change much until Hench discovered a “miracle drug” in 1949.

scholarly journals Cross-tissue, single-cell stromal atlas identifies shared pathological fibroblast phenotypes in four chronic inflammatory diseases

2021 ◽  
Author(s):  
Ilya Korsunsky ◽  
Kevin Wei ◽  
Mathilde Pohin ◽  
Edy Y. Kim ◽  
Francesca Barone ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Inflammatory Bowel Disease ◽  
Single Cell ◽  
Intestinal Inflammation ◽  
Inflammatory Diseases ◽  
Chronic Inflammatory Disease ◽  
Chronic Inflammatory Diseases ◽  
Single Cell Rna Sequencing ◽  
Inflammatory Bowel ◽  
Novel Therapeutic

SummaryPro-inflammatory fibroblasts are critical to pathogenesis in rheumatoid arthritis, inflammatory bowel disease, interstitial lung disease, and Sjögren’s syndrome, and represent a novel therapeutic target for chronic inflammatory disease. However, the heterogeneity of fibroblast phenotypes, exacerbated by the lack of a common cross-tissue taxonomy, has limited the understanding of which pathways are shared by multiple diseases. To investigate, we profiled patient-derived fibroblasts from inflamed and non-inflamed synovium, intestine, lung, and salivary glands with single-cell RNA-sequencing. We integrated all fibroblasts into a multi-tissue atlas to characterize shared and tissue-specific phenotypes. Two shared clusters, CXCL10+CCL19+ immune-interacting and SPARC+COL3A1+ vascular-interacting fibroblasts were expanded in all inflamed tissues and additionally mapped to dermal analogues in a public atopic dermatitis atlas. We further confirmed these human pro-inflammatory fibroblasts in animal models of lung, joint, and intestinal inflammation. This work represents the first cross-tissue, single-cell fibroblast atlas revealing shared pathogenic activation states across four chronic inflammatory diseases.

scholarly journals Targeting interleukin-17 in chronic inflammatory disease: A clinical perspective

2019 ◽  
Vol 217 (1) ◽  
Author(s):  
Pascale Zwicky ◽  
Susanne Unger ◽  
Burkhard Becher
Keyword(s):  
Rheumatoid Arthritis ◽  
Inflammatory Diseases ◽  
Chronic Inflammatory Disease ◽  
Interleukin 17 ◽  
Clinical Perspective ◽  
Preclinical Models ◽  
Chronic Inflammatory Diseases ◽  
Recent Developments ◽  
Disease Entities ◽  
Barrier Tissues

Chronic inflammatory diseases like psoriasis, Crohn’s disease (CD), multiple sclerosis (MS), rheumatoid arthritis (RA), and others are increasingly recognized as disease entities, where dysregulated cytokines contribute substantially to tissue-specific inflammation. A dysregulation in the IL-23/IL-17 axis can lead to inflammation of barrier tissues, whereas its role in internal organ inflammation remains less clear. Here we discuss the most recent developments in targeting IL-17 for the treatment of chronic inflammation in preclinical models and in patients afflicted with chronic inflammatory diseases.

Can We Extrapolate Data from One Immune-Mediated Inflammatory Disease to Another One?

2019 ◽  
Vol 26 (2) ◽  
pp. 248-258 ◽  
Author(s):  
Fernando Magro ◽  
Rosa Coelho ◽  
Armando Peixoto
Keyword(s):  
Rheumatoid Arthritis ◽  
Inflammatory Diseases ◽  
Analytical Techniques ◽  
Approval Process ◽  
Homogeneous Population ◽  
Post Translational Modifications ◽  
Innovator Product ◽  
Immune Mediated ◽  
Bowel Diseases ◽  
Inflammatory Bowel

Immune-mediated inflammatory diseases share several pathogenic pathways and this pushes sometimes to extrapolate from one disease or indication to others. A biosimilar can be defined as a biotherapeutic product which is similar in terms of quality, safety, and efficacy to an already licensed reference biotherapeutic product. We review the substrate for extrapolation, the current approval process for biosimilars and the pioneering studies on biosimilars performed in rheumatoid arthritis patients. A biosimilar has the same amino acid sequence as its innovator product. However, post-translational modifications can occur and the current analytical techniques do not allow the final structure. To test the efficacy in one indication, a homogeneous population should be chosen and immunogenicity features are essential in switching and interchangeability. CT-P13 (Remsima™; Inflectra™) is a biosimilar of reference infliximab (Remicade®). It meets most of the requirements for extrapolation. Nevertheless, in inflammatory bowel diseases (IBD) we need more studies to confirm the postulates of extrapolation from rheumatoid arthritis and ankylosing spondylitis to IBD. Furthermore, an effective pharmacovigilance schedule is mandatory to look for immunogenicity and side effects.

Anti-inflammatory Activity of Extra Virgin Olive Oil Polyphenols: Which Role in the Prevention and Treatment of Immune-Mediated Inflammatory Diseases?

2017 ◽  
Vol 18 (1) ◽  
pp. 36-50 ◽  
Author(s):  
Carmela Santangelo ◽  
Rosaria Varì ◽  
Beatrice Scazzocchio ◽  
Patrizia De Sancti ◽  
Claudio Giovannini ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Multiple Sclerosis ◽  
Systemic Lupus Erythematosus ◽  
Phenolic Compounds ◽  
Lupus Erythematosus ◽  
Inflammatory Diseases ◽  
Virgin Olive Oil ◽  
Extra Virgin Olive Oil ◽  
Systemic Lupus ◽  
Inflammatory Bowel

Background and Objective: Altered inflammatory response characterizes chronic immunemediated inflammatory diseases (IMID) such as rheumatoid arthritis, inflammatory bowel disease, multiple sclerosis, systemic lupus erythematosus, and psoriasis. Accumulating evidence indicates that regular consumption of extra virgin olive oil (EVOO), the main source of fat in the Mediterranean diet, is associated with a reduced risk of developing chronic degenerative disorders such as cardiovascular diseases, type 2 diabetes and cancer. The beneficial effects on health of EVOO have been attributed, besides to the monounsaturated fats content, to the presence of phenolic compounds that have antioxidant, anti-inflammatory and immunomodulatory properties. The purpose of this review is to provide an overview of the effects of EVOO polyphenols on IMID highlighting the potential mechanisms of action. Methods: Scientific papers were found by searching in PubMed up to May 2017 using the following key words: rheumatoid arthritis, inflammatory bowel disease, multiple sclerosis, systemic lupus erythematosus, and psoriasis also in combination with EVOO, phenolic compounds, oleuropein, oleocantal, hydroxytyrosol,tyrosol and oleochantal. Results: In vitro and in vivo studies indicate that EVOO and its polyphenols can improve diseases symptoms in IMID, by acting both at local and systemic levels and by modulating several molecular pathways. Nevertheless, there are not sufficient data to achieve specific nutritional guidelines. Conclusion: Further research is needed to evaluate the real contribution of EVOO and its phenolic compounds in modulating the IMID-associated inflammatory perturbations, in order to develop appropriate nutritional recommendations.

FRI0564 SERUM LEVELS OF IL-6 AND IL-8 IN ANKYLOSING SPONDYLITIS PATIENTS: ASSOCIATIONS WITH DISEASE ACTIVITY

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 884.1-885
Author(s):  
E. Aleksandrova ◽  
A. Novikov ◽  
P. Kulakova ◽  
A. Dorofeev ◽  
N. Savenkova ◽  
...  
Keyword(s):  
New York ◽  
Ankylosing Spondylitis ◽  
Disease Activity ◽  
Heart Diseases ◽  
Elevated Serum ◽  
Serum Levels ◽  
Fecal Calprotectin ◽  
Chronic Inflammatory Disease ◽  
Control Group ◽  
Inflammatory Bowel

Background:Ankylosing spondylitis (AS) is a chronic inflammatory disease of the spine and sacroiliac joints characterized by new bone formation (syndesmophytes) and ankyloses. In AS cases, along with the damage to the musculoskeletal system, impairment of other organs and systems is often observed (uveitis, inflammatory bowel and heart diseases). Pro-inflammatory cytokines (TNF-α, IL-6,-17,-23,-21,-22,-31) and chemokines (IL-8) are key pathogenic markers in AS.Objectives:The aims of the study were to determine the serum levels of IL-6 and IL-8 in AS and investigate their relationship with disease activity.Methods:We studied 140 patients (pts) with AS fulfilled modified New York criteria (1984); (102M/38F); median and interquartile range (25th—75th percentile) of age 43.0; 35.0-51.0 years; disease duration 6.0; 4.0-12.0 years; BASDAI - 5.4; 4.1-6.6; ASDAS ESR - 3.6; 2.6-4.4; ASDAS CRP - 3.8; 2.7-4.5; 86% HLA-27 positive. In 50% of pts with AS, inflammatory bowel diseases (IBD) (Crohn’s disease and ulcerative colitis) were diagnosed. The control group included 17 healthy donors (HC). The serum concentrations of IL-6 and IL-8 were detected by chemiluminescence immunoassay using IMMULATE 1000 analyzer (Siemens Healthcare Diagnostics, USA).Results:AS pts had significantly higher serum level of IL-6 than HC (4.3; 0.1-8.0 pg/ml vs 2.3; 0.1-2.7 pg/ml, p <0.006). The median concentration of IL-8 didn’t differ between AS pts and HC (10.5; 8.3-18.0 pg/ml vs 11.9; 8.2-18.3 pg/ml, p>0.05). The same levels of IL-6 and IL-8 were detected in AS with IBD and AS without signs of IBD (p>0.05). In AS pts, serum IL-6 concentration was positively correlated with ASDAS ESR (r = 0.3), ASDAS CRP (r = 0.3), ESR (r = 0.3) and CRP (r = 0.5) (p <0.05); IL-8 was negatively associated with presence of fecal calprotectin (r = -0.3) (p <0.05).Conclusion:Elevated serum concentration of IL-6 in AS is associated with clinical and laboratory markers of high inflammatory activity of the disease. The levels of IL-8 in the sera of AS patients were negatively correlated with the concentration of fecal calprotectin. Data on the relationship of IL-8 with the activity of the pathological process in AS require further study.Disclosure of Interests:Elena Aleksandrova: None declared, Alexander Novikov: None declared, Polina Kulakova: None declared, Aleksey Dorofeev: None declared, Nadezhda Savenkova: None declared, Evgeniy Volnukhin: None declared, Anton Kovshik: None declared, Galina Lukina Speakers bureau: Novartis, Pfizer, UCB, Abbvie, Biocad, MSD, Roche

scholarly journals A Polymorphism ofORAI1rs7135617, Is Associated with Susceptibility to Rheumatoid Arthritis

2014 ◽  
Vol 2014 ◽  
pp. 1-5 ◽  
Author(s):  
Jeng-Hsien Yen ◽  
Che-Mai Chang ◽  
Yu-Wen Hsu ◽  
Chih-Hung Lee ◽  
Mei-Shin Wu ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Inflammatory Diseases ◽  
Case Control ◽  
Chronic Inflammatory Disease ◽  
Healthy Individuals ◽  
Taiwanese Population ◽  
Cellular Immune System ◽  
Genetic And Environmental Factors ◽  
Synovial Tissues ◽  
Cellular Immune

Rheumatoid arthritis (RA), a chronic inflammatory disease usually occurring in synovial tissues and joints, is highly associated with genetic and environmental factors.ORAI1, a gene related to cellular immune system, has been shown to be involved in the pathogenesis of chronic inflammatory diseases and immune diseases. To identify whetherORAI1gene contributes to RA susceptibility, we enrolled 400 patients with RA and 621 healthy individuals for a case-control genetic association study. Five tagging single nucleotides polymorphisms (tSPNs) withinORAI1gene were selected for genotyping. An SNP, rs7135617, showed a significant correlation with the risk of RA. Our results indicated that genetic polymorphism ofORAI1gene is involved in the susceptibility of RA in a Taiwanese population.

scholarly journals P795 Risk of incident paradoxical immune-mediated inflammatory diseases in patients with inflammatory bowel diseases treated with anti-TNF therapies: a nationwide Danish cohort study

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S625-S625
Author(s):  
D WARD ◽  
S Gørtz ◽  
N Nyboe Andersen ◽  
J Kirchgesner ◽  
T Jess
Keyword(s):  
Rheumatoid Arthritis ◽  
Cohort Study ◽  
Inflammatory Bowel Diseases ◽  
Hidradenitis Suppurativa ◽  
Inflammatory Diseases ◽  
Hazard Ratios ◽  
Immune Mediated ◽  
Bowel Diseases ◽  
Lag Period ◽  
Inflammatory Bowel

Abstract Background Tumour necrosis factor (TNF) has a central role in the pathophysiology of immune-mediated inflammatory diseases (IMIDs) including rheumatoid arthritis, psoriasis, hidradenitis suppurativa, and inflammatory bowel diseases (IBD). However, there have been case reports of patients receiving an anti-TNF therapy for one IMID subsequently developing a second IMID. We conducted a nationwide cohort study investigating the risk of incident IMID following anti-TNF exposure in patients with IBD in Denmark. Methods We followed patients with IBD from 1 January 2005 or date of IBD diagnosis (whichever occurred last) to an outcome event including incident diagnosis of hidradenitis suppurativa, arthropathic psoriasis, other forms of psoriasis, or rheumatoid arthritis; or emigration, death or 31 December 2018 (whichever occurred first). Patients were defined as exposed after a 3-month lag period from first anti-TNF infusion throughout follow-up, analogous to an intention-to-treat design. The lag period was censored from analyses to avoid including incipient IMIDs, unlikely to be caused by newly initiated anti-TNF treatment. We excluded patients initiating anti-TNF or with an outcome diagnosis before either 1 January 2005 or IBD diagnosis. We used Cox regression models with age as the underlying timescale, and sex, type of IBD (Crohn’s disease or ulcerative colitis), and calendar period of IBD diagnosis (in 5 year groups) as strata to estimate hazard ratios for each outcome, comparing anti-TNF users and non-users. Results Incidence rates (and 95% confidence intervals [CI]) as events per 100 000 person-years among anti-TNF users and non-users were, respectively, 138 (109–173) and 25.6 (22.0–29.7) for hidradenitis suppurativa, 26.3 (15.6–44.4) and 7.81 (5.95–10.2) for arthropathic psoriasis, 1177 (1085–1277) and 204 (121–189) for other forms of psoriasis, and 152 (121–189) and 95.6 (88.5–103) for rheumatoid arthritis. Hazard ratios (and 95% C.I.) were increased for hidradenitis suppurativa 2.91 (2.15–3.94), arthropathic psoriasis 2.62 (1.40–4.93), other forms of psoriasis 4.76 (4.27–5.31), and rheumatoid arthritis 2.35 (1.83–3.01). Conclusion The results indicate that patients with IBD receiving anti-TNF have an increased risk of IMIDs. An almost 5-fold increase in the risk of psoriasis is consistent with previous reports of psoriasiform skin lesions related to anti-TNF use. However, as more severe IBD is likely to be associated with both initiating anti-TNF and the incidence of other inflammatory diseases, the results are subject to confounding by indication. Thus, these results should be considered preliminary, and we plan to further address confounding by using propensity score methods.

scholarly journals Glucocorticoid dose-dependent risk of type 2 diabetes in six immune-mediated inflammatory diseases: a population-based cohort analysis

2020 ◽  
Vol 8 (1) ◽  
pp. e001220
Author(s):  
Jianhua Wu ◽  
Sarah L Mackie ◽  
Mar Pujades-Rodriguez
Keyword(s):  
Rheumatoid Arthritis ◽  
Type 2 Diabetes ◽  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Inflammatory Diseases ◽  
Population Based ◽  
Immune Mediated ◽  
Inflammatory Bowel ◽  
Dose Dependent

IntroductionIn immune-mediated inflammatory diseases, there is a lack of -estimates of glucocorticoid dose–response diabetes risk that consider changes in prescribed dose over time and disease activity.Research design and methodsPopulation-based longitudinal analysis of electronic health records from the UK Clinical Practice Research Datalink, linked to hospital admissions and the mortality registry (1998–2017). We included 100 722 adult patients without diabetes history, diagnosed with giant cell arteritis or polymyalgia rheumatica (n=32 593), inflammatory bowel disease (n=29 272), rheumatoid arthritis (n=28 365), vasculitis (n=6082), or systemic lupus erythematosus (n=4410). We estimated risks and HRs of type 2 diabetes associated with time-variant daily and total cumulative prednisolone-equivalent glucocorticoid dose using Cox regression methods.ResultsAverage patient age was 58.6 years, 65 469 (65.0%) were women and 8858 (22.6%) had a body mass index (BMI) ≥30 kg/m2. Overall, 8137 (8.1%) people developed type 2 diabetes after a median follow-up of 4.9 years. At 1 year, the cumulative risk of diabetes increased from 0.9% during periods of non-use to 5.0% when the daily prednisolone-equivalent dose was ≥25.0 mg. We found strong dose-dependent associations for all immune-mediated diseases, BMI levels and underlying disease duration, even after controlling for periods of active systemic inflammation. Adjusted HR for a <5.0 mg daily dose versus non-use was 1.90, 95% CI 1.44 to 2.50; range 1.70 for rheumatoid arthritis to 2.93 for inflammatory bowel disease.ConclusionsWe report dose-dependent risks of type 2 diabetes associated with glucocorticoid use for six common immune-mediated inflammatory diseases. These results underline the need for regular diabetic risk assessment and testing during glucocorticoid therapy in these patients.

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