Tumor necrosis factor-α plays an initiating role in extracorporeal circulation-induced acute lung injury.
BACKGROUND
Despite advances in critical care, the mortality rate for patients with acute lung injury (ALI) remains high. The aim of this study was to test the hypothesis that tumor necrosis factor-α (TNF-α) plays an initiating role in the onset of extracorporeal circulation (ECC)-induced ALI.


METHODS
Eight New Zealand rabbits subjected to 1 h of ECC and 40 min of observation after termination of ECC were used for monitoring pulmonary nociceptor activity. Fifty Sprague-Dawley (SD) rats that received 2 h of ECC and 4 h of rest were used to measure the pulmonary function and inflammatory cytokines release, including total cells, neutrophils, and TNF-α in bronchoalveolar lavage (BAL) and white blood cell (WBC) and neutrophils in blood. An additional 40 SD rats were randomized to pretreatment with inhalation of phosphate buffer solution (control group), IgG (IgG inh group), or TNF-α antibody (anti-TNF-α inh group) and venous injection of TNF-α antibody (anti-TNF-α iv group). After 2 h of ECC and 4 h of rest, the arterial blood and BAL fluid were collected for measurement of arterial oxygen pressure (PaO2) and inflammatory cytokines release. The left-lower-lung tissues of animals were stained with hematoxylin & eosin (H&E).


RESULTS
The results demonstrated that the activities of airway nociceptor and TNF-α release were similarly upregulated at the early stage and in a time-related manner in ECC-induced ALI. Pretreatment with TNF-α antibody inhalation, but not venous injection, improved pulmonary function, inhibited pulmonary inflammation, and attenuated pulmonary histopathological changes after ECC.


CONCLUSIONS
We concluded that TNF-α played an important role in the pathogenesis of ALI and acted as an initiating cytokine at the early stage of ECC-induced ALI.
Department of Anesthesiology and Translational Neuroscience Center, West China Hospital, Sichuan University, Chengdu, 610041, China.
Tao
T
Li
Nanfu
N
Luo
Lei
L
Du
Jing
J
Zhou
Jie
J
Zhang
Lina
L
Gong
Nenggang
N
Jiang
D055371:Acute Lung Injury / Q000097:blood / Q000276:immunology* / Q000503:physiopathology / Q000517:prevention & control; D000280:Administration, Inhalation; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D004195:Disease Models, Animal; D005112:Extracorporeal Circulation / Q000009:adverse effects*; D018836:Inflammation Mediators / Q000378:metabolism*; D007275:Injections, Intravenous; D008168:Lung / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D009504:Neutrophils / Q000276:immunology; D009619:Nociceptors / Q000378:metabolism; D010100:Oxygen / Q000097:blood; D011014:Pneumonia / Q000097:blood / Q000276:immunology* / Q000503:physiopathology / Q000517:prevention & control; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000378:metabolism*
D000893:Anti-Inflammatory Agents; D000911:Antibodies, Monoclonal; D018836:Inflammation Mediators; D014409:Tumor Necrosis Factor-alpha; D010100:Oxygen