Tocilizumab attenuates acute lung and kidney injuries and improves survival in a rat model of sepsis via down-regulation of NF-κB/JNK: a possible role of P-glycoprotein

Ibrahim, Yasmine F.; Moussa, Rabab A.; Bayoumi, Asmaa M. A.; Ahmed, Al-Shaimaa F.

doi:10.1007/s10787-019-00628-y

Cited by 76Sepsis Diagnosis and TreatmentAcute Kidney Injury ResearchInflammation biomarkers and pathways

Tocilizumab attenuates acute lung and kidney injuries and improves survival in a rat model of sepsis via down-regulation of NF-κB/JNK: a possible role of P-glycoprotein

Ibrahim, Yasmine F., Moussa, Rabab A., Bayoumi, Asmaa M. A., Ahmed, Al-Shaimaa F.·2020·Inflammopharmacology

DOI 10.1007/s10787-019-00628-y

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Abstract

Acute lung injury (ALI) and acute kidney injury (AKI) are major causes of sepsis-induced mortality. The objective of the study is to evaluate the effect of tocilizumab (TCZ), an IL-6 receptor inhibitor, in sepsis-induced ALI and AKI using the cecal ligation and puncture (CLP) rat model of sepsis. Clinical and experimental studies have demonstrated the importance of IL-6 in sepsis; however, the role of TCZ has not been investigated. Rats subjected to CLP developed histological evidence of ALI and AKI at 24 h. We found that TCZ alleviated sepsis-induced ALI and AKI as evidenced by improvements in various pathological changes, a significant reduction in the lung wet/dry weight ratio and total protein content in bronchoalveolar lavage fluid (BALF), and a significant decrease in the elevated serum level of creatinine (CR) and blood urea nitrogen (BUN). TCZ induced an increase in the survival rate of treated rats. Additionally, TCZ markedly inhibited sepsis-induced pulmonary and renal inflammatory responses. Moreover, we found that treatment with TCZ inhibited oxidative stress and apoptosis in lung and kidney tissue. TCZ treatment significantly inhibited NF-κB activation, attenuating JNK signaling pathway and significantly up-regulated P-glycoprotein (P-gp) expression in pulmonary as well as in renal tissues. Our data provide novel evidence that TCZ has a protective effect against sepsis-induced ALI and AKI by blocking IL-6 receptor signaling. This could provide a molecular basis f…

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ARDS and renal dysfunction induced in a sepsis rat model are suppressed by anti-IL-6R antibody through the suppression of NF-κB activation.
“Furthermore, it has been shown that ARDS and renal dysfunction induced in a sepsis rat model are suppressed by anti-IL-6R antibody through the suppression of NF-κB activation (356).”
From IL-6 in inflammation, autoimmunity and cancer (2021) · cites this paper as [356]

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Authors: Ibrahim, Y. F., Moussa, R. A., Bayoumi, A. M. A., & Ahmed, A.-S. F.
Affiliations: Minia University (EG)
Corresponding author: Ahmed, Al-Shaimaa F.
ORCID: Ibrahim, Yasmine F.
Moussa, Rabab A.
Bayoumi, Asmaa M. A.
Ahmed, Al-Shaimaa F.
Venue: Inflammopharmacology
Publisher: Springer Science and Business Media LLC
Published: 2019-08-22
Volume: 28
Issue: 1
Pages: 215-230
ISSN: 0925-4692 (ISSN-L)
1568-5608
DOI: 10.1007/s10787-019-00628-y
OpenAlex: W2969893880
Cited by: 75
References: 77
Citations by year: 2026: 6 · 2025: 8 · 2024: 8 · 2023: 15 · 2022: 14 · 2021: 12 · 2020: 10 · 2019: 2
FWCI: 7.29
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
Locations: Inflammopharmacology (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health
Topics: Health Sciences › Medicine › Epidemiology › Sepsis Diagnosis and Treatment
Health Sciences › Medicine › Nephrology › Acute Kidney Injury Research
Life Sciences › Immunology and Microbiology › Immunology › Inflammation biomarkers and pathways
Keywords: tocilizumab, sepsis, acute lung injury, acute kidney injury, IL-6 receptor inhibition, NF-κB signaling, JNK signaling, P-glycoprotein, oxidative stress, apoptosis, cecal ligation and puncture, renal inflammation, lung inflammation, survival
MeSH terms: Animals, Female, Kidney, Lung, Signal Transduction, Down-Regulation, NF-kappa B, Rats, Wistar, Sepsis, ATP Binding Cassette Transporter, Subfamily B, Member 1, MAP Kinase Signaling System, Rats, Acute Lung Injury, Acute Kidney Injury, Antibodies, Monoclonal, Humanized

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Tocilizumab attenuates acute lung and kidney injuries and improves survival in a rat model of sepsis via down-regulation of NF-κB/JNK: a possible role of P-glycoprotein

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