Protective properties of inhaled IL-22 in a model of ventilator-induced lung injury.
High-pressure ventilation induces barotrauma and pulmonary inflammation, thus leading to ventilator-induced lung injury (VILI). IL-22 has both immunoregulatory and tissue-protective properties. Functional IL-22 receptor expression is restricted to nonleukocytic cells, such as alveolar epithelial cells. When applied via inhalation, IL-22 reaches the pulmonary system directly and in high concentrations, and may protect alveolar epithelial cells against cellular stress and biotrauma associated with VILI. In A549 lung epithelial cells, IL-22 was able to induce rapid signal transducer and activator of transcription (STAT)-3 phosphorylation/activation, and hereon mediated stable suppressor of cytokine signaling (SOCS) 3 expression detectable even 24 hours after onset of stimulation. In a rat model of VILI, the prophylactic inhalation of IL-22 before induction of VILI (peak airway pressure = 45 cm H(2)O) protected the lung against pulmonary disintegration and edema. IL-22 reduced VILI-associated biotrauma (i.e., pulmonary concentrations of macrophage inflammatory protein-2, IL-6, and matrix metalloproteinase 9) and mediated pulmonary STAT3/SOCS3 activation. In addition, despite a short observation period of 4 hours, inhaled IL-22 resulted in an improved survival of the rats. These data support the hypothesis that IL-22, likely via activation of STAT3 and downstream genes (e.g., SOCS3), is able to protect against cell stretch and pulmonary baro-/biotrauma by enhancing epithelial cell resistibility.
Hoegl
Sandra
S
Clinic for Anesthesiology, University Hospital of Ludwig-Maximilians-University, Munich, Germany. sandra.hoegl@med.uni-muenchen.de
Bachmann
Malte
M
Scheiermann
Patrick
P
Goren
Itamar
I
Hofstetter
Christian
C
Pfeilschifter
Josef
J
Zwissler
Bernhard
B
Muhl
Heiko
H
D000336:Aerosols / Q000378:metabolism; D000818:Animals; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000166:cytology; D006801:Humans; D007249:Inflammation; D007378:Interleukins / Q000378:metabolism*; D008168:Lung / Q000378:metabolism; D008175:Lung Neoplasms / Q000378:metabolism; D008297:Male; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D050796:STAT3 Transcription Factor / Q000378:metabolism; D055397:Ventilator-Induced Lung Injury / Q000378:metabolism*; D000097043:Interleukin-22
D000336:Aerosols; D007378:Interleukins; D050796:STAT3 Transcription Factor; D000097043:Interleukin-22; C494086:STAT3 protein, human; C494088:Stat3 protein, rat