Effects of Tocilizumab, an Interleukin-6 Receptor Antagonist, on Cytokine Expression and Animal Survival in a Model of Fatal Acute Respiratory Distress Syndrome
https://doi.org/10.33647/2074-5982-16-4-60-70
Abstract
This study aims to investigate effects of tocilizumab, a monoclonal antibody to interleukin-6 (IL-6) receptors, on cytokine expression and animal survival in a model of fatal acute respiratory distress syndrome (ARDS) characterized by high mortality rates and increased IL-6 production in the lungs. The expression of interleukin-1β (IL-1β), interleukin-6 (IL-6), tumour necrosis factor (TNF-α) and interferons α (IFN-α) and β (IFN-β) in the lungs was assessed by real-time PCR. Cytokine production was assessed by enzyme immunoassay. Although tocilizumab did not affect the expression of the studied cytokines in the lungs of animals with ARDS, it changed the profiles of their release. An acute multifold increase in the levels of IL-6 in the lungs was observed in the first two hours after the administration of tocilizumab, followed by a decrease of IL-6 to lower values similar to those observed in intact animals. Tocilizumab did not reduce mortality in treated animals with ARDS compared to those without treatment. Thus, the inhibition of the IL-6 receptor signaling pathway alone does not provide an effective solution to the problem of reducing mortality from ARDS associated with the development of a “cytokine storm”.
About the Authors
V. N. Karkischenko
Scientific Center of Biomedical Technologies of the Federal Medical and Biological Agency of Russia
Russian Federation
Russian Federation
Vladislav N. Karkischenko, Dr. Sci. (Med.), Prof.
143442, Moscow region, Krasnogorsk district, Svetlye gory village, building 1
I. A. Pomytkin
Scientific Center of Biomedical Technologies of the Federal Medical and Biological Agency of Russia
Russian Federation
Russian Federation
Igor A. Pomytkin, Cand. Sci. (Chem.)
143442, Moscow region, Krasnogorsk district, Svetlye gory village, building 1
N. V. Petrova
Scientific Center of Biomedical Technologies of the Federal Medical and Biological Agency of Russia
Russian Federation
Russian Federation
Nataliya V. Petrova
143442, Moscow region, Krasnogorsk district, Svetlye gory village, building 1
S. V. Maksimenko
Scientific Center of Biomedical Technologies of the Federal Medical and Biological Agency of Russia
Russian Federation
Russian Federation
Sergey V. Maksimenko, Cand. Sci. (Biol.)
143442, Moscow region, Krasnogorsk district, Svetlye gory village, building 1
M. M. Skripkina
Scientific Center of Biomedical Technologies of the Federal Medical and Biological Agency of Russia
Russian Federation
Russian Federation
Mariya M. Skripkina
143442, Moscow region, Krasnogorsk district, Svetlye gory village, building 1
A. I. Levashova
Scientific Center of Biomedical Technologies of the Federal Medical and Biological Agency of Russia
Russian Federation
Russian Federation
Anna I. Levashova, Cand. Sci. (Chem.)
143442, Moscow region, Krasnogorsk district, Svetlye gory village, building 1
S. E. Dengina
Scientific Center of Biomedical Technologies of the Federal Medical and Biological Agency of Russia
Russian Federation
Russian Federation
Svetlana E. Dengina
143442, Moscow region, Krasnogorsk district, Svetlye gory village, building 1
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Review
For citations:
Karkischenko V.N., Pomytkin I.A., Petrova N.V., Maksimenko S.V., Skripkina M.M., Levashova A.I., Dengina S.E. Effects of Tocilizumab, an Interleukin-6 Receptor Antagonist, on Cytokine Expression and Animal Survival in a Model of Fatal Acute Respiratory Distress Syndrome. Journal Biomed. 2020;16(4):60-70. (In Russ.) https://doi.org/10.33647/2074-5982-16-4-60-70
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