Reevaluation of Lung Injury in TNF-Induced Shock: The Role of the Acid Sphingomyelinase
Joint Authors
Reiss, Lucy Kathleen
Uhlig, Stefan
Drescher, Hannah
Raffetseder, Ute
Gibbert, Lydia
Streetz, Konrad L.
Schwarz, Agatha
Martin, Christian
Adam, Dieter
Source
Issue
Vol. 2020, Issue 2020 (31 Dec. 2020), pp.1-14, 14 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2020-05-01
Country of Publication
Egypt
No. of Pages
14
Main Subjects
Abstract EN
Tumor necrosis factor (TNF) is a well-known mediator of sepsis.
In many cases, sepsis results in multiple organ injury including the lung with acute respiratory distress syndrome (ARDS).
More than 20-year-old studies have suggested that TNF may be directly responsible for organ injury during sepsis.
However, these old studies are inconclusive, because they relied on human rather than conspecific TNF, which was contaminated with endotoxin in most studies.
In this study, we characterized the direct effects of intravenous murine endotoxin-free TNF on cardiovascular functions and organ injury in mice with a particular focus on the lungs.
Because of the relevance of the acid sphingomyelinase in sepsis, ARDS, and caspase-independent cell death, we also included acid sphingomyelinase-deficient (ASM-/-) mice.
ASM-/- and wild-type (WT) mice received 50 μg endotoxin-free murine TNF intravenously alone or in combination with the pan-caspase inhibitor carbobenzoxy-valyl-alanyl-aspartyl-[O-methyl]-fluoromethylketone (zVAD) and were ventilated at low tidal volume while lung mechanics were followed.
Blood pressure was stabilized by intra-arterial fluid support, and body temperature was kept at 37°C to delay lethal shock and to allow investigation of blood gases, lung histopathology, proinflammatory mediators, and microvascular permeability 6 hours after TNF application.
Besides the lungs, also the kidneys and liver were examined.
TNF elicited the release of inflammatory mediators and a high mortality rate, but failed to injure the lungs, kidneys, or liver of healthy mice significantly within 6 hours.
Mortality in WT mice was most likely due to sepsis-like shock, as indicated by metabolic acidosis, high procalcitonin levels, and cardiovascular failure.
ASM-/- mice were protected from TNF-induced hypotension and reflex tachycardia and also from mortality.
In WT mice, intravenous exogenous TNF does not cause organ injury but induces a systemic inflammatory response with cardiovascular failure, in which the ASM plays a role.
American Psychological Association (APA)
Reiss, Lucy Kathleen& Raffetseder, Ute& Gibbert, Lydia& Drescher, Hannah& Streetz, Konrad L.& Schwarz, Agatha…[et al.]. 2020. Reevaluation of Lung Injury in TNF-Induced Shock: The Role of the Acid Sphingomyelinase. Mediators of Inflammation،Vol. 2020, no. 2020, pp.1-14.
https://search.emarefa.net/detail/BIM-1191692
Modern Language Association (MLA)
Reiss, Lucy Kathleen…[et al.]. Reevaluation of Lung Injury in TNF-Induced Shock: The Role of the Acid Sphingomyelinase. Mediators of Inflammation No. 2020 (2020), pp.1-14.
https://search.emarefa.net/detail/BIM-1191692
American Medical Association (AMA)
Reiss, Lucy Kathleen& Raffetseder, Ute& Gibbert, Lydia& Drescher, Hannah& Streetz, Konrad L.& Schwarz, Agatha…[et al.]. Reevaluation of Lung Injury in TNF-Induced Shock: The Role of the Acid Sphingomyelinase. Mediators of Inflammation. 2020. Vol. 2020, no. 2020, pp.1-14.
https://search.emarefa.net/detail/BIM-1191692
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1191692