%0 Journal Article
%T Role of endogenous IL-18 in the lung during endotoxin-induced systemic inflammation.
%A Takahara M
%A Aoyama-Ishikawa M
%A Shuno K
%A Yamauhi C
%A Miyoshi M
%A Maeshige N
%A Usami M
%A Yamada T
%A Osako T
%A Nakao A
%A Kotani J
%J Acute Med Surg
%V 1
%N 1
%D Jan 2014
%M 29930818
暂无%R 10.1002/ams2.6
%X UNASSIGNED: Overactivated neutrophils are causes of acute lung injury, which is a major clinical problem with significant morbidity and mortality in sepsis. Serum interleukin (IL)-18 levels correspond to severity of systemic inflammation.
UNASSIGNED: To elucidate the roles of endogenous IL-18 in lung injury during endotoxin-induced systemic inflammation.
UNASSIGNED: Wild-type (WT) and IL-18 gene knockout (KO) mice were injected with lipopolysaccharide (40 mg/kg) intraperitoneally and killed. Lungs were collected at 0 and 12 h to assess mRNA for intercellular adhesion molecule (ICAM)-1, inducible nitric oxide synthase, myeloperoxidase, immunohistochemistry (cleaved caspase-3, 8-hydroxy-2-deoxyguanosine), and wet/dry ratio. Blood was collected at 0, 1, 12, 18, and 24 h to assess plasma cytokine levels.
UNASSIGNED: The survival rates at 24 h were approximately 43% and 76% in the WT and KO mice, respectively. Plasma IL-18 levels were induced time-dependently only in the WT mice. Plasma interferon-γ levels were significantly higher in the WT than in the KO mice at 12 h, but IL-6 and tumor necrosis factor-α levels did not differ between the WT and KO mice. At 12 h, the WT mice showed higher myeloperoxidase activity (P < 0.05), ICAM-1, and wet/dry ratios than KO mice. Cleaved caspase-3 positive neutrophils, which migrated in the lung interstitium, were lower in WT mice than in KO mice.
UNASSIGNED: Endogenous IL-18 induced neutrophil accumulation, accompanied by induction of ICAM-1 expression, inhibition of neutrophil apoptosis, and increased inducible nitric oxide synthase-induced oxidative tissue injury in the lung, leading to lung edema and poor outcome during endotoxemia.