In this study we have compared the therapeutic effect of the administration of immunostimulatory DNA sequences (ISS) with that of corticosteroids on the resolution of airway inflammation and airway hyperreactivity (AHR) in a mouse model. Mice which had already developed significant levels of eosinophilic airway inflammation 24 h after allergen challenge were then treated with either ISS or corticosteroids, and the effect on AHR and airway inflammation assessed 6 d later. ISS inhibited AHR as effectively as corticosteroids. Combination therapy with ISS and corticosteroids was more effective than monotherapy with either ISS or corticosteroids in inhibiting AHR. In ovalbumin-challenged mice, levels of bronchoalveolar lavage (BAL) eosinophils were significantly reduced with either ISS or corticosteroids. ISS induced significant levels of BAL interferon-gamma, whereas corticosteroids did not induce expression of BAL interferon-gamma. Both ISS and corticosteroids significantly reduced levels of interleukin-5 in BAL, as well as the number of Periodic Acid Schiff-positive airway epithelial cells. Corticosteroids, but not ISS, increased the number of eosinophils in regional mediastinal lymph nodes. Very few apoptotic peribronchial cells were noted following ovalbumin challenge as assessed by TUNEL assay. Corticosteroids, but not ISS, induced an increase in the small number of apoptotic peribronchial cells. The mechanism by which either ISS or corticosteroids inhibit AHR is likely to be mediated by distinct and shared cellular pathways. The combination of the shared and distinct anti-inflammatory pathways may account for the additive effect of ISS and corticosteroids on inhibiting AHR.
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http://dx.doi.org/10.1165/rcmb.4853 | DOI Listing |
Brain Behav
October 2024
Department of Neurology, Johannes Kepler University Linz, Kepler University Hospital, Linz, Austria.
Adv Rheumatol
May 2024
Department of Medicine, The University of Melbourne at St Vincent's Hospital, 41 Victoria Parade, Fitzroy, Victoria, 3065, Australia.
Eur J Cancer
June 2024
Université Paris Saclay, AP-HP, Hôpital de Bicêtre, Department of Internal Medicine, UMR 1184, CEA INSERM, FHU CARE, Le Kremlin Bicêtre, France. Electronic address:
Background: Immune checkpoint blockers (ICBs) can induce immune-related adverse events (irAEs) whose management is based on expert opinion and may require the prescription of steroids and/or immunosuppressants (ISs). Recent data suggest that these treatments can reduce the effectiveness of ICBs.
Objective: To investigate the relationship between the use of steroids and/or ISs and overall survival (OS) and progression-free survival (PFS) among ICB-treated patients with an irAE.
Biosensors (Basel)
January 2024
Department of Chemistry "Giacomo Ciamician", Alma Mater Studiorum-University of Bologna, Tecnopolo di Rimini, Via Dario Campana 71, I-47922 Rimini, Italy.
One of the main challenges to be faced in deep space missions is to protect the health and ensure the maximum efficiency of the crew by preparing methods of prevention and in situ diagnosis. Indeed, the hostile environment causes important health problems, ranging from muscle atrophy, osteopenia, and immunological and metabolic alterations due to microgravity, to an increased risk of cancer caused by exposure to radiation. It is, therefore, necessary to provide new methods for the real-time measurement of biomarkers suitable for deepening our knowledge of the effects of space flight on the balance of the immune system and for allowing the monitoring of the astronaut's health during long-term missions.
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October 2023
Centre for Behavioural Sciences and Mental Health, Istituto Superiore di Sanità, Rome, Italy.
Cognitive flexibility involves the capability to switch between different perspectives and implement novel strategies upon changed circumstances. The Wisconsin Card Sorting Test (in humans) and the Attentional Set-Shifting Task (ASST, in rodents) evaluate individual capability to acquire a reward-associated rule and subsequently disregard it in favour of a new one. Both tasks entail consecutive stages wherein subjects discriminate between: two stimuli of a given category (simple discrimination, SD); the stimuli of SD confounded by an irrelevant stimulus of a different category (compound discrimination, CD); different stimuli belonging to the SD category (intradimensional shift, IDS); and two stimuli of the confounding category (extradimensional shift, EDS).
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