Effects of alpha 1-antitrypsin on endotoxin-induced lung inflammation in vivo

Research output: Contribution to journalArticle


Previous in vitro experiments demonstrated that acute-phase protein, alpha 1-antitrypsin (AAT), could act either as an enhancer or as a suppressor of lipopolysaccharide (LPS)-induced cell activation depending on treatment time. Here we investigate how AAT regulates inflammatory responses in the short term when administrated post LPS challenge. Similar experimental setup was used both in vitro and in vivo: human monocytes and neutrophils were stimulated with LPS for 2 h followed by AAT for a total time of 4 h, and C57BL/6 mice were treated intranasally with LPS and 2 h later with AAT and sacrificed after 4 h. Bronchial lavage (BAL) and lung homogenates were analyzed using bio-plex cytokine assay. BAL cell counts were assessed. Within 4 h, AAT enhanced LPS-induced tumor necrosis factor-alpha (TNF alpha), interleukin (IL)-6, and IL-8 release from monocytes and neutrophils. Mice challenged for 4 h with LPS followed by AAT at 2 h showed no changes in BAL cell counts and higher levels of almost all measured cytokines, specifically RANTES in BAL and IL-12, IL-13, granulocyte colony-stimulating factor (G-CSF), granulocyte macrophage colony-stimulating factor (GM-CSF), and IL-10 levels in lung homogenates, than in mice treated with LPS only. Within the short term, AAT enhances the magnitude of LPS-induced specific cytokine/chemokine production, which may play an important role in amplification and resolution of acute-phase inflammatory reactions in vivo.


  • Devipriya Subramaniyam
  • Chad Steele
  • Thomas Koehnlein
  • Tobias Welte
  • Olof Grip
  • Sadis Matalon
  • Sabina Janciauskiene
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Rheumatology and Autoimmunity


  • Inflammation, Cytokines, Alpha 1-antitrypsin, Endotoxin, Acute-phase proteins
Original languageEnglish
Pages (from-to)571-578
JournalInflammation Research
Issue number7
Publication statusPublished - 2010
Publication categoryResearch