Inhibiting IL-6 in COVID-19: we are not sure

Honoré, Patrick M.; Gutierrez, Leonel Barreto; Kugener, Luc; Redant, Sebastien; Attou, Rachid; Gallerani, Andrea; Bels, David De

doi:10.1186/s13054-020-03177-x

Cited by 11 publications

(10 citation statements)

References 8 publications

(14 reference statements)

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“…Blocking antibodies or small molecules targeting IL-6 or its signal transduction pathways have been used in the clinical trials to treat COVID-19 patients ( 23 , 29 ). However, targeting IL-6 signal transduction pathways might be complicated as IL-6 activates both pro-inflammatory pathway through the soluble form of the IL-6 receptor, and anti-inflammatory pathway through the membrane-bound form of the IL-6 receptor ( 27 , 44 ). IL-8 is clearly a pro-inflammatory cytokine that may recruit neutrophils to the infected areas and has been associated with tissue damage.…”

Section: Discussionmentioning

confidence: 99%

“…These reports suggest a possible connection between proinflammatory cytokine induction and adverse effects of COVID-19. IL-6 is considered a relevant indicator in predicting severe course of COVID-19 disease and target for COVID-19 treatment (27)(28)(29)(30)(31). Besides inflammatory cytokines, some other predictors, such as lymphocyte number, lactate dehydrogenase, D-dimer, and IL-2R have also been identified as out of normal range in COVID-19 patients (12,32,33).…”

Section: Introductionmentioning

confidence: 99%

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Interleukin-8 as a Biomarker for Disease Prognosis of Coronavirus Disease-2019 Patients

et al. 2021

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The widespread prevalence of coronavirus disease-2019 (COVID-19) which is caused by severe respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, has resulted in a severe global public health emergency. However, there are no sensitive biomarkers to predict the disease prognosis of COVID-19 patients. Here, we have identified interleukin-8 (IL-8) as a biomarker candidate to predict different disease severity and prognosis of COVID-19 patients. While serum IL-6 become obviously elevated in severe COVID-19 patients, serum IL-8 was easily detectible in COVID-19 patients with mild syndromes. Furthermore, lL-8 levels correlated better than IL-6 levels with the overall clinical disease scores at different stages of the same COVID-19 patients. Thus, our studies suggest that IL-6 and IL-8 can be respectively used as biomarkers for severe COVID-19 patients and for COVID-19 disease prognosis.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Interleukin-8 as a Biomarker for Disease Prognosis of Coronavirus Disease-2019 Patients

et al. 2021

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“…1 B) [ 78 ]. Sgp130Fc (Olamkicept) is a fusion protein of the extracellular domain of the gp130 receptor which is linked to the constant portion (Fc) of a human Ig G1 [ 79 ]. In this regard, sgp130Fc may be a selective inhibitor of IL-6 in COVID-19 infection and can be used as a specific substitute for tocilizumab.…”

Section: Application Of Monoclonal Antibodies Targeting Il-6 and Il-6rmentioning

confidence: 99%

COVID-19 infection: an overview on cytokine storm and related interventions

Montazersaheb

Khatibi

Hejazi

et al. 2022

Virol J

338

203

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Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has posed a significant threat to global health. This virus affects the respiratory tract and usually leads to pneumonia in most patients and acute respiratory distress syndrome (ARDS) in 15% of cases. ARDS is one of the leading causes of death in patients with COVID-19 and is mainly triggered by elevated levels of pro-inflammatory cytokines, referred to as cytokine storm. Interleukins, such as interleukin-6 (1L-6), interleukin-1 (IL-1), interleukin-17 (IL-17), and tumor necrosis factor-alpha (TNF-α) play a very significant role in lung damage in ARDS patients through the impairments of the respiratory epithelium. Cytokine storm is defined as acute overproduction and uncontrolled release of pro-inflammatory markers, both locally and systemically. The eradication of COVID-19 is currently practically impossible, and there is no specific treatment for critically ill patients with COVID-19; however, suppressing the inflammatory response may be a possible strategy. In light of this, we review the efficacy of specific inhibitors of IL6, IL1, IL-17, and TNF-α for treating COVID-19-related infections to manage COVID-19 and improve the survival rate for patients suffering from severe conditions. Graphical Abstract

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“…Furthermore, in the management of COVID-19, tocilizumab, which prevents sIL-6 and membrane-bound IL-6R from forming a complex with gp130, inhibits the pro-and anti-inflammatory pathways. Consequently, IL-6 inhibitors should be cautiously used to manage COVID-19 [51,68,69]. The classical IL-6 signaling system requires membrane-bound IL-6R, whose expression is limited to macrophages, neutrophils, T cells, and hepatocytes [70].…”

Section: Classical Signaling and Trans-signaling Of Il-6mentioning

confidence: 99%

Anti-Inflammatory Effect of Muscle-Derived Interleukin-6 and Its Involvement in Lipid Metabolism

Nara

Watanabe

2021

IJMS

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Interleukin (IL)-6 has been studied since its discovery for its role in health and diseases. It is one of the most important pro-inflammatory cytokines. IL-6 was reported as an exacerbating factor in coronavirus disease. In recent years, it has become clear that the function of muscle-derived IL-6 is different from what has been reported so far. Exercise is accompanied by skeletal muscle contraction, during which, several bioactive substances, collectively named myokines, are secreted from the muscles. Many reports have shown that IL-6 is the most abundant myokine. Interestingly, it was indicated that IL-6 plays opposing roles as a myokine and as a pro-inflammatory cytokine. In this review, we discuss why IL-6 has different functions, the signaling mode of hyper-IL-6 via soluble IL-6 receptor (sIL-6R), and the involvement of soluble glycoprotein 130 in the suppressive effect of hyper-IL-6. Furthermore, the involvement of a disintegrin and metalloprotease family molecules in the secretion of sIL-6R is described. One of the functions of muscle-derived IL-6 is lipid metabolism in the liver. However, the differences between the functions of IL-6 as a pro-inflammatory cytokine and the functions of muscle-derived IL-6 are unclear. Although the involvement of myokines in lipid metabolism in adipocytes was previously discussed, little is known about the direct relationship between nonalcoholic fatty liver disease and muscle-derived IL-6. This review is the first to discuss the relationship between the function of IL-6 in diseases and the function of muscle-derived IL-6, focusing on IL-6 signaling and lipid metabolism in the liver.

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Inhibiting IL-6 in COVID-19: we are not sure

Cited by 11 publications

References 8 publications

Interleukin-8 as a Biomarker for Disease Prognosis of Coronavirus Disease-2019 Patients

Interleukin-8 as a Biomarker for Disease Prognosis of Coronavirus Disease-2019 Patients

COVID-19 infection: an overview on cytokine storm and related interventions

Anti-Inflammatory Effect of Muscle-Derived Interleukin-6 and Its Involvement in Lipid Metabolism

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