Intratracheal antitumor necrosis factor-α antibody attenuates lung tissue damage following cardiopulmonary bypass

Artif Organs. 2013 Feb;37(2):142-9. doi: 10.1111/j.1525-1594.2012.01542.x. Epub 2013 Jan 18.

Abstract

The aim of this study is to investigate the protective effect and underlying mechanism of antitumor necrosis factor-α antibody (TNF-α Ab) on lung tissue injury after cardiopulmonary bypass (CPB). Twenty-eight healthy New Zealand white rabbits were randomly divided into four groups. Group I received only an open chest operation. Groups II-IV all received CPB. Furthermore, groups III and IV received post-CPB endotracheal intubation with phosphate buffered saline or TNF-α Ab (2400 pg/kg), respectively. Perioperative blood neutrophil count, TNF-α level, and malondialdehyde (MDA) levels were determined in both the right and left atriums. Lung water content, TNF-α messenger RNA, protein, apoptosis in situ, and pathomorphological changes were also measured. The results show that TNF-α Ab can significantly inhibit leukocyte accumulation, reduce secretion of TNF-α and MDA, decrease lung tissue apoptosis, and attenuate post-CPB pathomorphological changes. TNF-α Ab administration, however, cannot suppress the expression of TNF-α, suggesting that the protective effects of TNF-α Ab originate from inhibiting the numerous biological functions of TNF-α. Intratracheal TNF-α Ab administration demonstrates a notable protective effect against lung injury after CPB.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies / administration & dosage*
  • Apoptosis / drug effects
  • Blotting, Western
  • Cardiopulmonary Bypass / adverse effects*
  • Disease Models, Animal
  • Drug Administration Routes
  • Intubation, Intratracheal
  • Leukocyte Count
  • Lung / drug effects*
  • Lung / immunology
  • Lung / pathology
  • Lung Injury / genetics
  • Lung Injury / immunology
  • Lung Injury / pathology
  • Lung Injury / prevention & control*
  • Malondialdehyde / metabolism
  • Neutrophils / drug effects
  • Neutrophils / immunology
  • RNA, Messenger / metabolism
  • Rabbits
  • Reverse Transcriptase Polymerase Chain Reaction
  • Time Factors
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Antibodies
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha
  • Malondialdehyde