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

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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.

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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

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Supplementary files

Supplementary Files
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1. 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

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2. 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

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3. 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

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Copyright (c) 2021 Aleksandrov A.G.

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