Changes in inspiratory effort in severe hypoxia against the backdrop of interleukin-6 and tumor necrosis factor

Authors

DOI:

https://doi.org/10.33910/2687-1270-2022-3-3-359-366

Keywords:

proinflammatory cytokines, acute respiratory distress syndrome, hypoxia, inspiratory effort, intra-thoracic pressure, breathing pattern

Abstract

Today, it is paramount to clarify the role of proinflammatory cytokines in the acute respiratory distress syndrome (ARDS) with severe hypoxemia and systemic inflammatory reaction (SIR). Previously, we found that an increase in the number of circulating IL-1ß and TNF-α suppressing the compensatory reaction of pulmonary ventilation to hypoxia is the main cause of respiratory failure and reduced survival after hypoxic apnea. IL-6 does not cause respiratory decompensation in severe hypoxia, instead, it increases the risk of mortality compared to IL-1ß and TNF-α. We suggested that this difference in the nature of respiratory reactions may be due to the opposite biological effects that cytokines have on the generation of inspiratory effort which is indicative of the activity of respiratory muscles. We conducted a comparative assessment of the effect of intravenous administration of IL-6 and TNF-α on the generation of inspiratory effort (intra-thoracic pressure) and the breathing pattern in hypoxia. In anesthetized rats hypoxia was reproduced by the rebreathing method from normoxia up to apnea. The data were analyzed at FIO2 8%. The recorded parameters include respiratory volume (Vt), breathing frequency (BF), minute lung ventilation (MLV), esophageal pressure (Pes), and survival after hypoxic apnea. It was found that in severe hypoxia IL-6 does not suppress the generation of inspiratory effort and the activity of the respiratory muscles, hence, it does not lead to decompensation of the respiratory function. TNF-α contributes to the development of acute respiratory failure due to the weakening of the inspiratory effort and its contribution to the formation of the breathing pattern.

References

Behrens, E. M., Koretzky, G. A. (2017) Review: Cytokine storm syndrome: Looking toward the precision medicine era. Arthritis and Rheumatol, vol. 69, no. 6, pp. 1135–1143. https://doi.org/10.1002/art.40071 (In English)

Dall’Ago, P., Chiappa, G. R. S., Guths, H. et al. (2006) Inspiratory muscle training in patients with heart failure and inspiratory muscle weakness: A randomized trial. Journal of the American College of Cardiology, vol. 47, no. 4, pp. 757–763. https://doi.org/10.1016/j.jacc.2005.09.052 (In English)

Donina, Zh. A., Baranova, E. V., Aleksandrova, N. P. (2021) Sravnitel’naya otsenka vliyaniya osnovnykh mediatorov ostrofazovogo otveta (IL-1, FNO-α i IL-6) na pattern dykhaniya i vyzhivaemost’ krys pri ostroj narastayushchej gipoksii [Comparative assessment of the effect of the main mediators of acute phase response (IL-1, TNF-a i IL-6) na pattern dykhaniya i vyzhivaemost’ krys pri ostroj narastayushchej gipoksii [Comparative assessment of the effect of the main mediators of acute phase response (IL-1, TNF-a and IL-6) on breathing pattern and survival in rats with acute progressive hypoxia]. Rossiiskij fiziologicheskij zhurnal imeni I. M. Sechenova, vol. 107, no. 8, pp. 996–1006. https://doi.org/10.31857/S0869813921080045 (In Russian)

Harris, T. B., Ferrucci, L., Tracy, R. P. et al. (1999) Associations of elevated interleukin-6 and C-reactive protein levels with mortality in the elderly. American Journal of Medicine, vol. 106, no. 5, pp. 506–512. https://doi.org/10.1016/s0002-9343(99)00066-2 (In English)

Henry, B. M., de Oliveira, M. H. S., Benoit, S. et al. (2020) Hematologic, biochemical and immune biomarker abnormalities associated with severe illness and mortality in coronavirus disease 2019 (COVID-19): A meta-analysis. Clinical Chemistry Laboratory Medicine, vol. 58, no. 7, pp. 1021–1028. https://doi.org/10.1515/cclm-2020-0369 (In English)

Hsieh, Y.-H., Litvin, D. G., Zaylor, A. R. et al. (2020) Brainstem inflammation modulates the ventilatory pattern and its variability after acute lung injury in rodents. The Journal of Physiology, vol. 598, no. 13, pp. 2791–2811. https://doi.org/10.1113/JP279177 (In English)

Jacono, F. J., Mayer, C. A., Hsieh, Y-H., et al. (2011) Lung and brainstem cytokine levels are associated with breathing pattern changes in a rodent model of acute lung injury. Respiratory Physiology and Neurobiology, vol. 178, no. 3, pp. 429–438. https://doi.org/10.1016/j.resp.2011.04.022 (In English)

Janssen, S. P. M., Gayan-Ramirez, G., Bergh, A. V. et al. (2005) Interleukin-6 causes myocardial failure and skeletal muscle atrophy in rats. Circulation, vol. 111, no. 8, pp. 996–1005. https://doi.org/10.1161/01.CIR.0000156469.96135.0D (In English)

Jiang, J., Yang, B, Han, G. et al (2015) Early administration of cisatracurium attenuates sepsis-induced diaphragm dysfunction in rats. Inflammation, vol. 38, no. 1, pp. 305–311. https://doi.org/10.1007/s10753-014-0034-8 (In English)

Liu, B. W., Li, M., Zhou, Z. G. et al. (2020) Can we use interleukin-6 (IL-6) blockade for coronavirus disease 2019 (COVID-19)-induced cytokine release syndrome (CRS)? Journal of Autoimmunity, vol. 111, article 102452. https://doi.org/10.1016/j.jaut.2020.102452 (In English)

Liu, X., He, L., Stensaas, L. et al. (2009) Adaptation to chronic hypoxia involves immune cell invasion and increased expression of inflammatory cytokines in rat carotid body. American Journal of Physiology-Lung Cellular and Molecular Physiology, vol. 296, no. 2, pp. 158–166. https://doi.org/10.1152/ajplung.90597.2008 (In English)

Moriya, J. (2019) Critical roles of inflammation in atherosclerosis. Journal of Cardiology, vol. 73, no. 1, pp. 22–27. https://doi.org/10.1016/j.jjcc.2018.05.010 (In English)

Park, W. Y., Goodman, R. B., Steinberg, K. P. et al. (2001) Cytokine balance in the lungs of patients with acute respiratory distress syndrome. American Journal of Respiratory and Critical Care Medicine, vol. 164, no. 10, pp. 1896–1903. https://doi.org/10.1164/ajrccm.164.10.2104013 (In English)

Pedersen, B. K., Akerstrom, T. C. A., Nielsen, A. R., Fischer, C. P. (2007) Role of myokines in exercise and metabolism. Journal of Applied Physiology, vol. 103, no. 3, pp. 1093–1098. https://doi.org/10.1152/japplphysiol.00080.2007 (In English)

Petersen, A. M., Pedersen, B. K. (2005) The anti-inflammatory effect of exercise. Journal of Applied Physiology, vol. 98, no. 4, pp. 1154–1162. https://doi.org/10.1152/japplphysiol.00164.2004 (In English)

Probert, L. (2015) TNF and its receptors in the CNS: The essential, the desirable and the deleterious effects. Neuroscience, vol. 302, pp. 2–22. https://doi.org/10.1016/j.neuroscience.2015.06.038 (In English)

Somers, E. C., Eschenauer, G. A., Troost, J. P. et al. (2020) Tocilizumab for treatment of mechanically ventilated patients with COVID-19. Clinical Infection Diseases, vol. 73, no. 2, pp. e445–e454. https://doi.org/10.1093/cid/ciaa954 (In English)

Spiesshoefer, J., Henke, C., Kabitz, J. H. et al. (2021) Heart failure results in inspiratory muscle dysfunction irrespective of left ventricular ejection fraction. Respiration, vol. 100, no. 2, pp. 96–108. https://doi.org/10.1159/000509940 (In English)

Takagishi, M., Waki, H., Bhuiyan, M. E. et al. (2010) IL-6 microinjected in the nucleus tractus solitarii attenuates cardiac baroreceptor reflex function in rats. American Journal of Physiology. Regulatory, Integrative and Comparative Physiology, vol. 298, no. 1, pp. 183–190. https://doi.org/10.1152/ajpregu.00176.2009 (In English)

Trushina, E. Yu., Kostina, E. M., Molotilov, B. A. et al. (2019) Rol’ tsitokinov IL-4, IL-6, IL-8, IL-10 v immunopatogeneze khronicheskoj obstruktivnoj bolezni legkikh [Role of il-4, il-6, il-8, il-10 cytokines in the immunopathogenesis of chronic obstructive pulmonary disease]. Meditsinskaya immunologiya — Medical Immunology, vol. 21, no. 1, pp. 89–98. https://doi.org/10.15789/1563-0625-2019-1-89-98 (In Russian)

Vaporidi, K., Akoumianaki, E., Telias, I. et al (2020) Respiratory drive in critically ill patients. Pathophysiology and clinical implications. American Journal of Respiratory and Critical Care Medicine, vol. 201, no. 1, pp. 20–32. https://doi.org/10.1164/rccm.201903-0596SO (In English)

Vassilakopoulos, T., Hussain, S. N. (2007) Ventilatory muscle activation and inflammation: cytokines, reactive oxygen species, and nitric oxide. Journal Applied Physiology, vol. 102, no. 4, pp. 1687–1695. https://doi.org/10.1152/japplphysiol.01273.2006 (In English)

Verity, R., Okell, L., Dorigatti, I., Winskill, P et al. (2020) Estimates of the severity of coronavirus disease 2019: A model-based analysis. The Lancet Infectious Diseases, vol. 20, no. 6, pp. 669–677. https://doi.org/10.1016/S1473-3099(20)30243-7 (In English)

Zhang, J., Cheng, X., Liao, Y. H. et al. (2005) Simvastatin regulates myocardial cytokine expression and improves ventricular remodeling in rats after acute myocardial infarction. Cardiovascular Drugs and Therapy, vol. 19, no. 1, pp. 13–21. https://doi.org/10.1007/s10557-005-6893-3 (In English)

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Published

2022-11-30

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Vol. 3 No. 3 (2022)

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Experimental articles

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Copyright (c) 2022 Elizaveta V. Baranova, Zhanna A. Donina

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