Study of Recombinant Interleukin-1 Receptor Antagonist Compositions Biological Activity After Injection and Inhalation in Mouse Model of Pulmonary Inflammation
- Authors: Ischenko A.M.1, Nekrasova K.A.1, Laptev D.S.2, Bobkov D.V.2, Kolobov A.A.2, Simbirtsev A.S.1
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Affiliations:
- State Research Institute of Highly Pure Biopreparations
- Research Institute of Hygiene, Occupational Pathology and Human Ecology
- Issue: Vol 21, No 3 (2024)
- Pages: 153-161
- Section: Original Study Articles
- URL: https://cijournal.ru/1684-7849/article/view/643495
- DOI: https://doi.org/10.17816/CI643495
- EDN: https://elibrary.ru/CPTDJX
- ID: 643495
Cite item
Abstract
BACKGROUND: The severity of respiratory distress syndrome is associated with the development of systemic multifactorial inflammatory processes leading to hyperinflammation. Proinflammatory cytokines, primarily interleukin-1 (IL-1), and reactive oxygen species substantially contribute to these pathological processes. The use of an interleukin-1 receptor antagonist (IL-1Ra) as an IL-1 blocker is a key first-line therapy for patients experiencing cytokine storm syndrome. The novelty of the approach under investigation lies in studying the effectiveness of inhaled administration of IL-1Ra, including its combined use with a reactive oxygen species inhibitor — superoxide dismutase (SOD).
AIM: To assess the efficacy of IL-1Ra administered parenterally and by inhalation, both as a standalone agent and in combination with SOD, in a bleomycin-induced acute respiratory distress syndrome model.
MATERIALS AND METHODS: Male BALB/c mice were used in the study. Respiratory distress syndrome was modeled by intraperitoneal administration of bleomycin at a dose of 2 mg/mouse on days 1, 8, and 15 of the experiment. The investigational drugs—a 10.0-mg/mL IL-1Ra solution and a 10.0-mg/mL IL-1Ra solution containing 0.4 mg/mL SOD—were administered to the experimental groups either subcutaneously or by inhalation at a dose of 2 mg/mouse daily for 15 days starting from day 1 of the experiment. Body weight, spirometry, histological studies, and animal survival were assessed.
RESULTS: Subcutaneous and inhalation administration of IL-1Ra + SOD, as well as subcutaneous administration of IL-1Ra, positively affected animal survival. Subcutaneous administration of IL-1Ra and IL-1Ra + SOD led to statistically significant improvements in indicators of external respiration in mice with bleomycin-induced intoxication. A reduction in destructive lung changes caused by intraperitoneal administration of bleomycin was observed in the experimental groups receiving inhaledIL-1Ra orIL-1Ra + SOD and in the group receiving subcutaneous IL-1Ra.
CONCLUSION: Both investigational products — IL-1Ra and IL-1Ra + SOD — administered by injection or inhalation demonstrated a positive effect in the treatment of respiratory distress syndrome induced by bleomycin in the mouse model.
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About the authors
Alexander M. Ischenko
State Research Institute of Highly Pure Biopreparations
Email: amischenko1946@mail.ru
ORCID iD: 0000-0002-6661-6145
SPIN-code: 5860-4216
Cand. Sci. (Biology)
Russian Federation, Saint PetersburgKsenia A. Nekrasova
State Research Institute of Highly Pure Biopreparations
Author for correspondence.
Email: k.a.nekrasova@hpb.spb.ru
ORCID iD: 0000-0002-0242-9615
SPIN-code: 9435-6100
Cand. Sci. (Biology)
Russian Federation, Saint PetersburgDenis S. Laptev
Research Institute of Hygiene, Occupational Pathology and Human Ecology
Email: laptev@gpech.ru
ORCID iD: 0000-0002-3960-3058
SPIN-code: 2873-5071
Cand. Sci. (Biology)
Russian Federation, Saint PetersburgDmitry V. Bobkov
Research Institute of Hygiene, Occupational Pathology and Human Ecology
Email: bobkov@gpech.ru
ORCID iD: 0000-0003-3989-0437
SPIN-code: 2673-8240
Russian Federation, Saint Petersburg
Alexander A. Kolobov
Research Institute of Hygiene, Occupational Pathology and Human Ecology
Email: aak1959@internet.ru
ORCID iD: 0000-0002-9222-6773
SPIN-code: 7019-2420
Dr. Sci. (Biology)
Russian Federation, Saint PetersburgAndrey S. Simbirtsev
State Research Institute of Highly Pure Biopreparations
Email: a.s.simbirtsev@hpb.spb.ru
ORCID iD: 0000-0002-8228-4240
SPIN-code: 2064-7584
MD, Dr. Sci. (Medicine), Professor
Russian Federation, Saint PetersburgReferences
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