Interleukin-6 does not upregulate pro-inflammatory cytokine expression in an ex vivo model of giant cell arteritis

Objective: The aim of this study was to examine the pro-inflammatory effects of IL-6 in ex vivo temporal artery explant cultures. Methods: Patients meeting 1990 ACR classification criteria for GCA were prospectively recruited. Temporal artery biopsies were obtained and temporal artery explants cultured ex vivo with IL-6 (10-40 ng/ml) in the presence or absence of its soluble receptor (sIL-6R; 20 ng/ml) for 24 h. Explant supernatants were harvested after 24 h and assayed for IFN-γ, TNF-α, Serum amyloid A, IL-1β, IL-17, IL-8, angiotensin II and VEGF by ELISA. Myofibroblast outgrowths, cytoskeletal rearrangement and wound repair assays were performed. Results: IL-6 augmented production of VEGF, but not of any of the other pro-inflammatory mediators assayed. No differences were observed in the explants cultured in the presence or absence of the sIL-6R or between those with a positive (n = 11) or negative (n = 17) temporal artery biopsy. IL-6 did not enhance myofibroblast proliferation or migration. Western blot analysis confirmed signalling activation, with increased expression of pSTAT3 in response to IL-6+sIL-6R. Conclusion: IL-6 stimulation of temporal artery explants from patients with GCA neither increased expression of key pro-inflammatory mediators nor influenced myofibroblast proliferation or migration.</p

Outcomes of COVID-19 in people with rheumatic and musculoskeletal disease in Ireland over the first 2 years of the pandemic

Background: Poor COVID-19 outcomes occur with higher frequency in people with rheumatic and musculoskeletal diseases (RMD). Better understanding of the factors involved is crucial to informing patients and clinicians regarding risk mitigation. Aim: To describe COVID-19 outcomes for people with RMD in Ireland over the first 2 years of the pandemic. Methods: Data entered into the C19-GRA provider registry from Ireland between 24th March 2020 and 31st March 2022 were analysed. Differences in the likelihood of hospitalisation and mortality according to demographic and clinical variables were investigated. Results: Of 237 cases included, 59.9% were female, 95 (41.3%) were hospitalised, and 22 (9.3%) died. Hospitalisation was more common with increasing age, gout, smoking, long-term glucocorticoid use, comorbidities, and specific comorbidities of cardiovascular and pulmonary disease, and cancer. Hospitalisation was less frequent in people with inflammatory arthritis and conventional synthetic or biologic disease-modifying antirheumatic drug use. Hospitalisation had a U-shaped relationship with disease activity, being more common in both high disease activity and remission. Mortality was more common with increasing age, gout, smoking, long-term glucocorticoid use, comorbidities, and specific comorbidities of cardiovascular disease, pulmonary disease, and obesity. Inflammatory arthritis was less frequent in those who died. Conclusion: Hospitalisation or death were more frequently experienced by RMD patients with increasing age, certain comorbidities including potentially modifiable ones, and certain medications and diagnoses amongst other factors. These are important 'indicators' that can help risk-stratify and inform the management of RMD patients.</p

Temporal trends in COVID-19 outcomes in people with rheumatic diseases in Ireland: data from the COVID-19 global rheumatology alliance registry

Objectives: Although evidence is accumulating globally, data on outcomes in rheumatic disease and COVID-19 in Ireland are limited. We used data from the COVID-19 Global Rheumatology Alliance (C19-GRA) to describe time-varying COVID-19 outcomes for people with rheumatic disease in Ireland.Methods: Data entered into the C19-GRA provider registry from Ireland between 24th March 2020 and 9th July 2021 were analysed. Differences in the likelihood of hospitalisation and mortality according to demographic and clinical variables were investigated using Chi-squared test or Fisher's exact test, as appropriate. Trends in odds of hospitalisation and mortality over time were investigated using logistic regression with the time period as a categorical variable.Results: Of 212 cases included, 59.4% were female and median age was 58.0 years (range 13-96). Of the 212 cases, 92 (43%) were hospitalized and 22 (10.4%) died. Increasing age, a diagnosis of gout, ever smoking, glucocorticoid use, having comorbidities, and specific comorbidities of cancer, cardiovascular, and pulmonary disease were more common in those hospitalised. A diagnosis of inflammatory arthritis, csDMARD and/or b/tsDMARD use were less frequent in those hospitalised. Increasing age, a diagnosis of gout, ever smoking, having comorbidities and specific comorbidities of obesity, cardiovascular and pulmonary disease were more common in those who died. Odds of hospitalisation or mortality did not change over time.Conclusion: No temporal trend was observed in either COVID-19 related hospitalisation or mortality outcomes for people with rheumatic disease in Ireland.</div