We report two cases of cytomegalovirus (CMV) viraemia resulting in severe pneumonitis and associated haemophagocytic syndrome manifesting in patients with inflammatory bowel disease, on stable doses of azathioprine in clinical remission. In both cases, azathioprine was withdrawn at time of hospital presentation and after delays in diagnosis; intravenous ganciclovir was then administered, with resultant rapid improvement of haematological and clinical parameters. Following recovery, immunomodulators were not recommenced given patient aversion and the theoretical risk of CMV reactivation, albeit the evidence for this approach is limited. CMV-related haemophagocytic syndrome and organ dysfunction, in the context of immunomodulator therapy in IBD are rare but life-threatening, and thus requires further investigation and discussion.
Inflammasomes are multi-protein complexes that sense both infectious and sterile inflammatory stimuli, launching a cascade of responses to propagate danger signaling throughout an affected tissue. Recent studies have implicated inflammasome activation in a variety of pulmonary diseases, including pulmonary arterial hypertension (PAH). Indeed, the end-products of inflammasome activation, including interleukin (IL)-1β, IL-18, and lytic cell death (“pyroptosis”) are all key biomarkers of PAH, and are potentially therapeutic targets for human disease. This review summarizes current knowledge of inflammasome activation in immune and vascular cells of the lung, with a focus on the role of these pathways in the pathogenesis of PAH. Special emphasis is placed on areas of potential drug development focused on inhibition of inflammasomes and their downstream effectors.
Innate immune cells such as neutrophils respond to signals at sites of infection or tissue damage by moving to the affected area and eliminating microbes by producing reactive oxygen species (ROS), very reactive molecules that damage and kill microbes, and neutrophil extracellular traps (NETs), expelled DNA chromatin and histones that form net‐like structures with sticky surfaces that can trap and kill microbes. Although ROS and NET formation are needed to prevent life‐threatening infections, excessive inflammation can lead to host tissue damage and dysfunction, and, indeed, does so in many types of diseases. Chlorogenic acid (CGA), a dietary polyphenol found in coffee, has antioxidant and potentially anti‐inflammatory effects. The possible anti‐inflammatory impacts of CGA have important medical implications due to the widespread, global availability of coffee, even in areas with reduced access to affordable and accessible pharmaceuticals. We tested the impacts of CGA on PMA‐induced ROS and NET formation in neutrophil‐like HL‐60 cells. We found that CGA functions as an antioxidant that significantly decreases PMA‐induced ROS production cells in these cells without affecting the production of superoxide or the formation of NETs. This suggests that CGA may function as an antioxidant in vivo and thereby reduce inflammation by decreasing the tissue‐damaging functions of ROS in inflamed tissues. We are currently investigating this idea further by elucidating the impact of chlorogenic acid on Lipopolysaccharide (LPS)‐induced ROS production by human polymorphonuclear neutrophils (PMN) to determine whether CGA maintains similar effects in a more physiological system.Support or Funding InformationDePauw University and the Science Research Fellows programThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.