PMID- 31902854
OWN - NLM
STAT- MEDLINE
DCOM- 20200903
LR  - 20200903
IS  - 1347-3409 (Electronic)
IS  - 1345-4676 (Linking)
VI  - 87
IP  - 3
DP  - 2020 Jul 13
TI  - Intravenous Immunoglobulin Attenuates Cecum Ligation and Puncture-Induced Acute 
      Lung Injury by Inhibiting Apoptosis of Alveolar Epithelial Cells.
PG  - 129-137
LID - 10.1272/jnms.JNMS.2020_87-303 [doi]
AB  - PURPOSE: Intravenous immunoglobulin (IVIG) therapy has been used to treat sepsis, 
      but its mechanisms of action remain unclear. Sepsis causes multiple organ 
      failure, such as acute lung injury (ALI), which involves apoptosis of alveolar 
      epithelial cells. In this study, we hypothesized that IVIG suppresses apoptosis 
      in alveolar epithelial cells and evaluated mortality, cytokine levels, 
      histological changes in the lung, and alveolar epithelial cell apoptosis after 
      IVIG administration, in mice with experimentally induced sepsis. METHODS: Mice 
      received an injection of vehicle (saline) or immunoglobulin (100 mg/kg or 400 
      mg/kg) into the tail vein, after which they underwent cecal ligation and 
      puncture. A sham-operated group was used as the normal control. Survival was 
      assessed in all groups after 72 hours. Plasma levels of TNF-alpha and IL-6, 
      histopathological changes and wet-to-dry ratio in lung, and alveolar epithelial 
      cell apoptosis were evaluated in all groups at 4 hours after surgery. RESULTS: In 
      the vehicle group, histopathological injury of the lung was severe, and apoptosis 
      of alveolar epithelial cells was significant. Survival and plasma cytokine levels 
      were better in the IVIG treatment groups than in the vehicle group. IVIG 400 
      mg/kg suppressed apoptosis of alveolar epithelial cells and reduced ALI. 
      CONCLUSION: IVIG suppressed inflammatory cytokine levels and improved survival. 
      Lung histopathology and alveolar epithelial cell apoptosis were improved by IVIG 
      treatment, in a dose-dependent manner. Suppressing apoptosis in alveolar 
      epithelial cells appears to be a mechanism by which IVIG improves survival.
FAU - Hagiwara, Jun
AU  - Hagiwara J
AD  - Department of Emergency and Critical Care Medicine, Graduate School of Medicine, 
      Nippon Medical School.
FAU - Yamada, Marina
AU  - Yamada M
AD  - Faculty of Medical Science, Nippon Sport Science University.
FAU - Motoda, Norio
AU  - Motoda N
AD  - Department of Pathology, Nippon Medical School Musashi Kosugi Hospital.
FAU - Yokota, Hiroyuki
AU  - Yokota H
AD  - Department of Emergency and Critical Care Medicine, Graduate School of Medicine, 
      Nippon Medical School.
LA  - eng
PT  - Journal Article
DEP - 20191227
PL  - Japan
TA  - J Nippon Med Sch
JT  - Journal of Nippon Medical School = Nippon Ika Daigaku zasshi
JID - 100935589
RN  - 0 (Immunoglobulins, Intravenous)
RN  - 0 (Inflammation Mediators)
RN  - 0 (Interleukin-6)
RN  - 0 (Tumor Necrosis Factor-alpha)
SB  - IM
MH  - Acute Lung Injury/*drug therapy/*etiology
MH  - Animals
MH  - Apoptosis/*drug effects
MH  - *Cecum
MH  - Dose-Response Relationship, Drug
MH  - Immunoglobulins, Intravenous/*administration & dosage/*pharmacology
MH  - Inflammation Mediators/blood
MH  - Interleukin-6
MH  - Ligation/*adverse effects
MH  - Male
MH  - Mice, Inbred C57BL
MH  - Pulmonary Alveoli/*drug effects/*pathology
MH  - Punctures/*adverse effects
MH  - Tumor Necrosis Factor-alpha/blood
OTO - NOTNLM
OT  - animal
OT  - apoptosis of alveolar epithelial cells
OT  - intravenous immunoglobulin
OT  - sepsis
EDAT- 2020/01/07 06:00
MHDA- 2020/09/04 06:00
CRDT- 2020/01/07 06:00
PHST- 2020/01/07 06:00 [pubmed]
PHST- 2020/09/04 06:00 [medline]
PHST- 2020/01/07 06:00 [entrez]
AID - 10.1272/jnms.JNMS.2020_87-303 [doi]
PST - ppublish
SO  - J Nippon Med Sch. 2020 Jul 13;87(3):129-137. doi: 10.1272/jnms.JNMS.2020_87-303. 
      Epub 2019 Dec 27.