Intravenous immunoglobulin attenuates cecum ligation and puncture -induced acute lung injury by inhibiting apoptosis of alveolar epithelial cells

Abstract

Purpose: Intravenous immunoglobulin (IVIG) therapy has been used to treat sepsis patients, but its detailed mechanism of action remains unclear. Sepsis causes multiple organ failure such as acute lung injury (ALI). The mechanism of ALI involves apoptosis of alveolar epithelial cells. In this study, we hypothesized that IVIG suppresses apoptosis in alveolar epithelial cells. We evaluated mortality, cytokine levels, histological changes in the lung, and alveolar epithelial cell apoptosis following IVIG administration to mice with experimentally induced sepsis.

Methods: Mice were administrated either 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 group after 72 hours. Plasma levels of TNF-α and IL-6, histopathological changes and wet-to-dry ratio of lung, and alveolar epithelial cell apoptosis were evaluated in all groups 4 hours after surgery.

Results: In the vehicle group, the histopathological injury of the lung was severe, and significant apoptosis of alveolar epithelial cells was observed. Both survival and plasma cytokine levels were improved in each of the IVIG treatment groups compared to the vehicle group. IVIG at 400 mg/kg suppressed apoptosis of alveolar epithelial cells and reduced ALI.

Conclusion: IVIG can suppress inflammatory cytokine levels and improve 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 one of the mechanisms by which IVIG improves survival.