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Bitte verwenden Sie diesen Link, wenn Sie dieses Dokument zitieren oder verlinken wollen: https://nbn-resolving.org/urn:nbn:de:gbv:9-opus-31174

IL-37 Causes Excessive Inflammation and Tissue Damage in Murine Pneumococcal Pneumonia

  • Streptococcus pneumoniae infections can lead to severe complications with excessive immune activation and tissue damage. Interleukin-37 (IL-37) has gained importance as a suppressor of innate and acquired immunity, and its effects have been therapeutic as they prevent tissue damage in autoimmune and inflammatory diseases. By using RAW macrophages, stably transfected with human IL-37, we showed a 70% decrease in the cytokine levels of IL-6, TNF-α, and IL-1β, and a 2.2-fold reduction of the intracellular killing capacity of internalized pneumococci in response to pneumococcal infection. In a murine model of infection with S. pneumoniae, using mice transgenic for human IL-37b (IL-37tg), we observed an initial decrease in cytokine expression of IL-6, TNF-α, and IL-1β in the lungs, followed by a late-phase enhancement of pneumococcal burden and subsequent increase of proinflammatory cytokine levels. Additionally, a marked increase in recruitment of alveolar macrophages and neutrophils was noted, while TRAIL mRNA was reduced 3-fold in lungs of IL-37tg mice, resulting in necrotizing pneumonia with augmented death of infiltrating neutrophils, enhanced bacteremic spread, and increased mortality. In conclusion, we have identified that IL-37 modulates several core components of a successful inflammatory response to pneumococcal pneumonia, which lead to increased inflammation, tissue damage, and mortality.

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Metadaten
Author: Anja E. Schauer, Tilman E. Klassert, Carolin von Lachner, Diana Riebold, Anne Schneeweiß, Magdalena Stock, Mario M. Müller, Sven Hammerschmidt, Philip Bufler, Ulrike Seifert, Kristina Dietert, Charles A. Dinarello, Marcel F. Nold, Achim D. Gruber, Claudia A. Nold-Petry, Hortense Slevogt
URN:urn:nbn:de:gbv:9-opus-31174
URL:http://www.karger.com/jin
DOI:https://doi.org/10.1159/000469661
ISSN:1662-811X
ISSN:1662-8128
Pubmed Id:https://pubmed.ncbi.nlm.nih.gov/28601872
Parent Title (English):Journal of Innate Immunity
Publisher:S. Karger AG
Place of publication:Basel, Switzerland
Document Type:Article
Language:English
Date of first Publication:2017/06/10
Release Date:2020/09/29
Tag:Antibacterial host defense; Immunosuppression; Inflammation; Interleukin-37; Pneumococcal pneumonia
GND Keyword:-
Volume:9
Issue:4
First Page:403
Last Page:418
Faculties:Universitätsmedizin / Institut für Med. Biochemie u. Molekularbiologie
Licence (German):License LogoUrheberrechtlich geschützt