Effects of Human Interleukin-10 on Ventilator-Associated Lung Injury in Rats
- 129 Downloads
Ventilator-induced lung injury (VILI) is one of the most serious complications of mechanical ventilation (MV) and can increase the mortality of patients with acute respiratory distress syndrome (ARDS). This work aimed to test the hypothesis that the anti-inflammatory properties of human interleukin-10 (hIL-10) can reduce VILI. Thirty-six healthy male Sprague-Dawley rats were randomly assigned into three groups (n = 12) as follows: a control group, a VILI group, and a hIL-10 group. Lung function was evaluated by oxygenation index and pulmonary edema, and morphological changes associated with lung injury were assessed by HE staining and quantitative histological lung injury score. Malondialdehyde (MDA) and Superoxide dismutase (SOD) were measured, and the levels of various inflammatory cytokines were assessed in BALF and plasma. The oxygenation index in the VILI group decreased significantly relative to the control group and improved substantially in the hIL-10 group (P < 0.01). Compared to the control group, MDA production was stimulated (P < 0.01), and SOD activity rapidly declined (P < 0.01) in the VILI group. After hIL-10, MDA content was lower than that seen in the VILI group (P < 0.01), and SOD activity was enhanced (P < 0.01). The VILI group had the highest cytokine levels, compared to either the hIL-10 group or the control group (P < 0.05). High tidal volume MV can induce VILI. hIL-10 may regulate the inflammatory response in the lung tissue, improve lung tissue oxygenation, and inhibit oxidative stress, therefore reducing VILI in rats. These experiments reveal a potential new treatment option for VILI.
Key Wordshuman interleukin-10 ventilator-associated lung injury mechanical ventilation
This work was supported by the Science and Technology Project of Education Department in Fujian Province (Project No. JK2014017), medical innovation program of Fujian Provincial Health Bureau (2016-CX-43).
Compliance with Ethical Standards
Conflict of Interest
The authors declare that they have no conflict of interest.
- 2.Moraes, L., C.L. Santos, R.S. Santos, F.F. Cruz, F. Saddy, M.M. Morales, V.L. Capelozzi, P.L. Silva, M.G. de Abreu, C.S. Garcia, P. Pelosi, and P.R. Rocco. 2014. Effects of sigh during pressure control and pressure support ventilation in pulmonary and extrapulmonary mild acute lung injury. Critical Care 18 (4): 474.CrossRefGoogle Scholar
- 4.Carvalho, N.C., A. Güldner, A. Beda, I. Rentzsch, C. Uhlig, S. Dittrich, P.M. Spieth, B. Wiedemann, M. Kasper, T. Koch, T. Richter, P.R. Rocco, P. Pelosi, and M.G. de Abreu. 2014. Higher levels of spontaneous breathing reduce lung injury in experimental moderate acute respiratory distress syndrome. Critical Care Medicine 42 (11): e702–e715.CrossRefGoogle Scholar
- 7.Severgnini, P., G. Selmo, C. Lanza, A. Chiesa, A. Frigerio, A. Bacuzzi, G. Dionigi, R. Novario, C. Gregoretti, M.G. de Abreu, M.J. Schultz, S. Jaber, E. Futier, M. Chiaranda, and P. Pelosi. 2013. Protective mechanical ventilation during general anesthesia for open abdominal surgery improves postoperative pulmonary function. Anesthesiology 118 (6): 1307–1321.CrossRefGoogle Scholar
- 8.Futier, E., J.M. Constantin, C. Paugam-Burtz, J. Pascal, M. Eurin, A. Neuschwander, E. Marret, M. Beaussier, C. Gutton, J.Y. Lefrant, B. Allaouchiche, D. Verzilli, M. Leone, A. De Jong, J.E. Bazin, B. Pereira, and S. Jaber. 2013. A trial of intraoperative low-tidal-volume ventilation in abdominal surgery. The New England Journal of Medicine 369 (5): 428–437.CrossRefGoogle Scholar
- 11.Koch, T. 1998. Origin and mediators involved in sepsis and the systemic inflammatory response syndrome. Kidney International. Supplement 64: S66–S69.Google Scholar
- 13.Halbertsma, F.J., M. Vaneker, G.J. Scheffer, and J.G. van der Hoeven. 2005. Cytokines and biotrauma in ventilator-induced lung injury: A critical review of the literature. The Netherlands Journal of Medicine 63 (10): 382–392.Google Scholar
- 14.Fu, W., P. Mao, R. Zhang, X.Q. Pang, H.Y. Mo, W.Q. He, X.Q. Liu, and Y.M. Li. 2013. Effects of cyclic stretch on expression of cytokines and intercellular adhesion molecule-1 in human pulmonary artery endothelial cell. Zhonghua Wei Zhong Bing Ji Jiu Yi Xue 25 (8): 484–488.Google Scholar
- 15.Kiss, T., P.L. Silva, R. Huhle, L. Moraes, R.S. Santos, N.S. Felix, C.L. Santos, M.M. Morales, V.L. Capelozzi, M. Kasper, P. Pelosi, M. Gama de Abreu, and P.R. Rocco. 2016. Comparison of different degree of variability in tidal volume to prevent deterioration of respiratory system elastance in experimental acute lung inflammation. British Journal of Anaesthesia 116 (5): 708–715.CrossRefGoogle Scholar
- 16.Kim, D.H., J.H. Chung, B.S. Son, Y.J. Kim, and S.G. Lee. 2014. Effect of a neutrophil elastase inhibitor on ventilator-induced lung injury in rats. J Thorac Dis 6 (12): 1681–1689.Google Scholar
- 21.Santiago VR, Rzezinski AF, Nardelli LM, Silva JD, Garcia CS, Maron-Gutierrez T, Ornellas DS, Morales MM, Capelozzi VL, Marini J, Pelosi P, Rocco PR: Recruitment maneuver in experimental acute lung injury: the role of alveolar collapse and edema. Crit Care Med 38(11): 2207–2214.Google Scholar
- 23.Papaiahgari, S., A. Yerrapureddy, S.R. Reddy, N.M. Reddy, J.M. Dodd-O, M.T. Crow, D.N. Grigoryev, K. Barnes, R.M. Tuder, M. Yamamoto, T.W. Kensler, S. Biswal, W. Mitzner, P.M. Hassoun, and S.P. Reddy. 2007. Genetic and pharmacologic evidence links oxidative stress to ventilator-induced lung injury in mice. American Journal of Respiratory and Critical Care Medicine 176 (12): 1222–1235.CrossRefGoogle Scholar
- 25.Zhang, J., Z.H. Tong, Z.Q. Qin, B.S. Pang, S.J. Niu, and C. Wang. 2010. Expression of intercellular cell adhesion molecule-1, interleukin-10 and the activation of activator protein-1 in ventilator-induced lung injury in rabbits. Zhonghua Jie He He Hu Xi Za Zhi 33 (8): 587–592.Google Scholar