The features of the course of virus-associated acute lung injury in mice with induced immunosuppression

Cover Page


Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription or Fee Access

Abstract

BACKGROUND: Among all groups of patients with virus-associated acute lung injury with influenza infection, the most severe course is observed in patients with immunosuppression. In this case, despite the studied mechanism of the course of combined pathology, the question of therapy in this group of patients remains unclear.

AIM: To study the features of the course of acute lung injury in influenza infection with secondary immunosuppression in an experiment for the possibility of searching for experimental therapy for this combined pathology.

MATERIALS AND METHODS: The study was performed on 115 outbred female mice. The mouse-adapted pandemic influenza virus A/California/7/09MA (H1N1)pdm09 was used for modeling viral acute lung injury. Experimental immunosuppression was reproduced by administration of methotrexate (1.25 mg/kg intraperitoneally, once every 3 days during 3 weeks before infection). During the experiment, mortality, blood oxygen saturation, the concentration of pro-inflammatory cytokines in the lungs, and the severity of lung injury were measured.

RESULTS: The presence of experimental immunosuppression led to an exacerbation of acute lung injury in infected animals in terms of mortality and lung damage. Changes in the dynamics of proinflammatory cytokines (TNF-á, IL-6, IL-1â) in the lungs were observed during acute lung injury. Retarded recovery of the lungs functional activity was noted.

CONCLUSIONS: The experimental immunosuppression contributed to the exacerbation of acute lung injury and to an increase in the duration of the pathology. These changes could be associated with an altered process of elimination of the pathogen. The reproduced model of combined pathology was used for searching a therapy for these complications.

Full Text

Restricted Access

About the authors

Andrey G. Aleksandrov

Smorodintsev Research Institute of Influenza

Author for correspondence.
Email: forphchemistry@gmail.com
ORCID iD: 0000-0001-9212-3865

Researcher

Russian Federation, Saint Petersburg

References

  1. Kozhokaru VI, Lobzin YuV, Kozhokaru DI. Intensive therapy of severe complications of influenza. Zurnal infektologii. 2012;4(1):58–64. (In Russ.). doi: 10.22625/2072-6732-2012-4-1-58-64
  2. Suratt BT, Parsons PE. Mechanisms of acute lung injury/acute respiratory distress syndrome. Clin Chest Med. 2006;27(4):579–589. doi: 10.1016/j.ccm.2006.06.005
  3. Harish MM, Ruhatiya RS. Influenza H1N1 infection in immunocompromised host: A concise review. Lung India. 2019;36(4):330–336. doi: 10.4103/lungindia.lungindia_464_18
  4. Cortegiani A, Madotto F, Gregoretti C, et al. Immunocompromised patients with acute respiratory distress syndrome: secondary analysis of the LUNG SAFE database. Crit Care. 2018;22(1):157. doi: 10.1186/s13054-018-2079-9
  5. Shitov LN. Vliyanie immunodepressantov na chislennost’ stafilokokkov v sostave mikroflory tolstoj kishki. Modern Problems of Science and Education. 2008;(1):151–152. (In Russ.)
  6. Matute-Bello G, Downey G, Moore BB, et al. An official American Thoracic Society workshop report: features and measurements of experimental acute lung injury in animals. Am J Respir Cell Mol Biol. 2011;44(5):725–738. doi: 10.1165/rcmb.2009-0210ST
  7. Zheng K, Wu L, He Z, et al. Measurement of the total protein in serum by biuret method with uncertainty evaluation. Measurement. 2017;112:16–21. doi: 10.1016/j.measurement.2017.08.013
  8. Patel BV, Wilson MR, Takata M. Resolution of acute lung injury and inflammation: a translational mouse model. Eur Respir J. 2011;39(5):1162–1170. doi: 10.1183/09031936.00093911
  9. Spadaro S, Park M, Turrini C, et al. Biomarkers for acute respiratory distress syndrome and prospects for personalised medicine. J Inflamm (Lond). 2019;16:1. doi: 10.1186/s12950-018-0202-y
  10. Okovityj SV. Klinicheskaya farmakologiya immunodepressantov. Reviews on Clinical Pharmacology and Drug Therapy. 2003;2(2):2–34. (In Russ.)

Supplementary files

Supplementary Files
Action
1. JATS XML
Download
2. Fig. 1. Kaplan–Meier survival curve (Mean ± SE, %). * р < 0,05 compared to group 1, Mantel–Cox test; # р < 0,05 compared to group 2, Mantel–Cox test. Group 1 — intact mice, group 2 — infected mice treated with phosphate-buffered saline, group 3 — infected mice with experimental immunosuppression

Download (70KB)
Indexing metadata
3. Fig. 2. Dynamic of saturation index during the experiment (Mean ± SE, %). * р < 0,05 compared to group 1, Mann–Whitney test; # р < 0,05 compared to group 2, Mann–Whitney test. Group 1 — intact mice, group 2 — infected mice treated with phosphate-buffered saline, group 3 — infected mice with experimental immunosuppression

Download (81KB)
Indexing metadata
4. Fig. 3. Lungs of infected mice on 4th and 7th days post infection. 1 — vascular plethora of the lungs; 2 — alveolar edema; 3 — hyaline membrane; 4 — cellular infiltrate; 5 — atelectasis; 6 — thickening of the alveolar septum. Staining with hematoxylin-eosin, magnificent ×100

Download (696KB)
Indexing metadata

Copyright (c) 2021 Aleksandrov A.G.

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).
Регистрационный номер и дата принятия решения о регистрации СМИ: серия ПИ № ФС 77 - 74760 от 29.12.2018 г.


This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies