Translating IL-6 biology into effective treatments

Choy, Ernest; Benedetti, Fabrizio; Takeuchi, Tsutomu; Hashizume, Misato; John, Markus R.; Kishimoto, Tadamitsu

doi:10.1038/s41584-020-0419-z

Cited by 488 publications

(383 citation statements)

References 159 publications

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“…Predictive biomarkers of clinical succeed using this MAb are currently investigated since some patients are not bene ted [27]. In addition, the use of this antibody should be managed with caution because the high risk of bacterial infection reported among its main adverse events [13].…”

Section: Discussionmentioning

confidence: 99%

An Anti-CD6 Monoclonal Antibody (Itolizumab) Reduces Circulating IL-6 in Severe Covid-19 Elderly Patients

Saavedra¹,

Añé-Kourí

Sánchez³

et al. 2020

Preprint

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Background: Since the COVID-19 outbreak an unprecedented challenge for healthcare systems around the world has been placed. In Cuba, the first case of COVID-19 was reported on March 11. Elderly with multiple comorbidities have been the most risky population. Although most patients present a mild to moderate disease, some have developed severe symptoms. One of the possible mechanisms underlying rapid disease progression is a cytokine storm, in which interleukin (IL) -6 seems to be a major mediator. Itolizumabis a humanized recombinant anti-CD6 monoclonal antibody(MAb), with the ability of reducingserum interferon gamma(INF-γ), tumournecrosis factor alpha(TNFα) and IL-6. Based on these previous results in patients with psoriasis and rheumatoid arthritis, an expanded access clinical trial was approved by the Cuban regulatory agency for COVID-19 critically, severely and moderately ill patients. Results: We show here a short kinetic of IL-6 serum concentration in the first 24 COVID-19 patients treated with itolizumab. Most of patients were elderly with multiple comorbidities.We found that with one itolizumabdose, the circulating IL-6 decreased in critically and severely ill patients, whereas in moderately ill patients the values didn’trise as compared to theirlow baseline levels.Conclusion: These findings suggest that itolizumabcould be an attractive therapeutic option to decrease the negative outcome of the cytokine storm in COVID-19 patients.Trial registration: CECMED IIC RD-EC 179, RPCEC00000311. Registered 4May 2020 - Retrospectively registered, http://rpcec.sld.cu/ensayos/RPCEC00000311-Sp or http://rpcec.sld.cu/trials/RPCEC00000311-En

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Section: Discussionmentioning

confidence: 99%

An Anti-CD6 Monoclonal Antibody (Itolizumab) Reduces Circulating IL-6 in Severe Covid-19 Elderly Patients

Saavedra¹,

Añé-Kourí

Sánchez³

et al. 2020

Preprint

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“…Soluble IL‐6, membrane‐bound IL‐6R, and gp130 can be part of the hexameric complex at the membrane, induce the IL‐6 signal transduction occurred through a high‐affinity complex of IL‐6/IL‐6R/gp130 (Choy et al, 2020). The results showed expression of IL6 had the same trend as IL6R at HepG2.…”

Section: Discussionmentioning

confidence: 99%

Co‐cultured bone marrow mesenchymal stem cells repair thioacetamide‐induced hepatocyte damage

Chen

Awale

et al. 2020

Cell Biology International

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Adult stem cells, such as bone marrow mesenchymal stem cells (BMSCs), are postdevelopmental cells found in many bone tissues. They are capable of multipotent differentiation and have low immune‐rejection characteristics. Hepatocytes may become inflamed and produce a large number of free radicals when affected by drugs, poisoning, or a viral infection. The excessive accumulation of free radicals in the extracellular matrix (ECM) eventually leads to liver fibrosis. This study aims to investigate the restorative effects of mouse bone marrow mesenchymal stem cells (mBMSCs) on thioacetamide (TAA)‐induced damage in hepatocytes. An in vitro transwell co‐culture system of HepG2 cells were co‐cultured with mBMSCs. The effects of damage done to TAA‐treated HepG2 cells were reflected in the overall cell survival, the expression of antioxidants (SOD1, GPX1, and CAT), the ECM (COL1A1 and MMP9), antiapoptosis characteristics (BCL2), and inflammation (TNF) genes. The majority of the damage done to HepG2 by TAA was significantly reduced when cells were co‐cultured with mBMSCs. The signal transducer and activator of transcription 3 (STAT3) and its phosphorylated STAT3 (p‐STAT3), as related to cell growth and survival, were detected in this study. The results show that STAT3 was significantly decreased in the TAA‐treated HepG2 cells, but the STAT3 and p‐STAT3 of HepG2 cells were significantly activated when the TAA‐treated HepG2 co‐cultured with mBMSCs. Strong expression of interleukin (Il6) messenger RNA in co‐cultured mBMSCs/HepG2 indicated mBMSCs secret the cytokines IL‐6, which promotes cell survival through downstream STAT3 activation and aid in the recovery of HepG2 cells damaged by TAA.

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“…As a proinflammatory cytokine, IL-6 has been shown to be involved in antibody production by B cells. 7 To assess this function in COVID-19, the association between IL-6 and humoral responses was evaluated in COVID-19 patients. As shown in Fig.…”

mentioning

confidence: 99%

Serum inflammatory factors are positively correlated with the production of specific antibodies in coronavirus disease 2019 patients

et al. 2020

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Translating IL-6 biology into effective treatments

Cited by 488 publications

References 159 publications

An Anti-CD6 Monoclonal Antibody (Itolizumab) Reduces Circulating IL-6 in Severe Covid-19 Elderly Patients

An Anti-CD6 Monoclonal Antibody (Itolizumab) Reduces Circulating IL-6 in Severe Covid-19 Elderly Patients

Co‐cultured bone marrow mesenchymal stem cells repair thioacetamide‐induced hepatocyte damage

Serum inflammatory factors are positively correlated with the production of specific antibodies in coronavirus disease 2019 patients

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