Transfection of IL-10 expression vectors into endothelial cultures attenuates α4β7-dependent lymphocyte adhesion mediated by MAdCAM-1

BACKGROUND: Enhanced expression of MAdCAM-1 (mucosal addressin cell adhesion molecule-1) is associated with the onset and progression of inflammatory bowel disease. The clinical significance of elevated MAdCAM-1 expression is supported by studies showing that immunoneutralization of MAdCAM-1, or its ligands reduce inflammation and mucosal damage in models of colitis. Interleukin-10 (IL-10) is an endogenous anti-inflammatory and immunomodulatory cytokine that has been shown to prevent inflammation and injury in several animal studies, however clinical IL-10 treatment remains insufficient because of difficulties in the route of IL-10 administration and its biological half-life. Here, we examined the ability of introducing an IL-10 expression vector into endothelial cultures to reduce responses to a proinflammatory cytokine, TNF-α METHODS: A human IL-10 expression vector was transfected into high endothelial venular ('HEV') cells (SVEC4-10); we then examined TNF-α induced lymphocyte adhesion to lymphatic endothelial cells and TNF-α induced expression of MAdCAM-1 and compared these responses to control monolayers. RESULTS: Transfection of the IL-10 vector into endothelial cultures significantly reduced TNF-α induced, MAdCAM-1 dependent lymphocyte adhesion (compared to non-transfected cells). IL-10 transfected endothelial cells expressed less than half (46 ± 6.6%) of the MAdCAM-1 induced by TNF-α (set as 100%) in non-transfected (control) cells. CONCLUSION: Our results suggest that gene therapy of the gut microvasculature with IL-10 vectors may be useful in the clinical treatment of IBD

Adaptation and response of a major Parisian referral hospital to the COVID-19 surge : a qualitative study

Since the beginning of the COVID-19 pandemic, few studies have focused on crisis management of multiple services within one hospital over several waves of the pandemic. The purpose of this study was to provide an overview of the COVID-19 crisis response of a Parisian referral hospital which managed the first three COVID cases in France and to analyze its resilience capacities. Between March 2020 and June 2021, we conducted observations, semi-structured interviews, focus groups, and lessons learned workshops. Data analysis was supported by an original framework on health system resilience. Three configurations emerged from the empirical data: 1) reorganization of services and spaces; 2) management of professionals' and patients' contamination risk; and 3) mobilization of human resources and work adaptation. The hospital and its staff mitigated the effects of the pandemic by implementing multiple and varied strategies, which the staff perceived as having positive and/or negative consequences. We observed an unprecedented mobilization of the hospital and its staff to absorb the crisis. Often the mobilization fell on the shoulders of the professionals, adding to their exhaustion. Our study demonstrates the capacity of the hospital and its staff to absorb the COVID-19 shock by putting in place mechanisms for continuous adaptation. More time and insight will be needed to observe whether these strategies and adaptations will be sustainable over the coming months and years and to assess the overall transformative capacities of the hospital