Supplementary Material for: IL-37 Causes Excessive Inflammation and Tissue Damage in Murine Pneumococcal Pneumonia
Schauer A.E.
Klassert T.E.
von Lachner C.
Riebold D.
Schneeweiß A.
Stock M.
Müller M.M.
Hammerschmidt S.
Bufler P.
Seifert U.
Dietert K.
Dinarello C.A.
Nold M.F.
Gruber A.D.
Nold-Petry C.A.
Slevogt H.
10.6084/m9.figshare.5097121.v1
https://karger.figshare.com/articles/dataset/Supplementary_Material_for_IL-37_Causes_Excessive_Inflammation_and_Tissue_Damage_in_Murine_Pneumococcal_Pneumonia/5097121
<p><i>Streptococcus pneumoniae </i>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 <i>S. pneumoniae</i>, 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.</p>
2017-06-09 07:52:22
Interleukin-37
Immunosuppression
Inflammation
Antibacterial host defense
Streptococcus pneumoniae
Pneumococcal pneumonia