Immune‐suppressive effects of interleukin‐6 on T‐cell‐mediated anti‐tumor immunity

Tsukamoto, Hirotake; Fujieda, Koji; Senju, Satoru; Ikeda, Tokunori; Oshiumi, Hiroyuki; Nishimura, Yasuharu

doi:10.1111/cas.13433

Cited by 124 publications

(86 citation statements)

References 59 publications

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“…In addition, Cygb-deficient mice show elevated TNF-α and IL-6 in tumor and non-tumor tissue of the liver and lung (Thuy et al, 2011). These findings indicate that Cygb deficiency can trigger inflammation, which may contribute to increased susceptibility to cancer development (Roh et al, 2003;Park et al, 2010;Tsukamoto et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

Cytoglobin Attenuates Neuroinflammation in Lipopolysaccharide-Activated Primary Preoptic Area Cells via NF-κB Pathway Inhibition

Gomes

Sousa

Ott

et al. 2019

Front. Mol. Neurosci.

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Cytoglobin (Cygb) is a hexacoordinate protein, associated with the transport of oxygen, nitric oxide scavenging, tumor suppression and protection against oxidative stress and inflammation. This protein is expressed in brain areas including the preoptic area (POA) of the anterior hypothalamus, the region responsible for the regulation of body temperature. In this study, we show that Cygb is upregulated in the rat hypothalamus 2.5 h and 5 h after intravenous administration of lipopolysaccharide (LPS). We investigated the effect of treatment with Cygb in POA primary cultures stimulated with LPS for 4 h. The levels of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) were measured and the results showed that Cygb reduced the concentrations of both cytokines. We further observed a decrease in immunoreactivity of the inflammatory transcription factor nuclear factor-κB (NF-κB), but not NF-IL6 and STAT3, in the nucleus of Cygb-treated POA cells. These findings suggest that Cygb attenuates the secretion of IL-6 and TNF-α in LPS-stimulated POA primary cultures via inhibition of the NF-κB signaling pathway, indicating that this protein might play an important role in the control of neuroinflammation and fever.

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Section: Discussionmentioning

confidence: 99%

Cytoglobin Attenuates Neuroinflammation in Lipopolysaccharide-Activated Primary Preoptic Area Cells via NF-κB Pathway Inhibition

Gomes

Sousa

Ott

et al. 2019

Front. Mol. Neurosci.

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“…IL-6 plays a prominent role in tumorigenesis and metastasis [108]. The modulation of immune cell function by IL-6 causes dysfunction of innate and adaptive immunity against tumors [109]. Therefore, the IL-6 targeting approach may desensitize and prevent the dysfunction of innate and adaptive immunity against tumors.…”

Section: Safety Of the Il-6 Inhibitor In Ramentioning

confidence: 99%

IL-6 inhibitor for the treatment of rheumatoid arthritis: A comprehensive review

Ogata

Kato

Higa

et al. 2019

Modern Rheumatology

166

124

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Tocilizumab (TCZ) is an interleukin-6 (IL-6) inhibitor used for the treatment of rheumatoid arthritis (RA). It was developed in 2008, and its effectiveness is supported by evidence from all over the world based on its first decade of use. Although the overall efficacy and safety profiles of TCZ are similar to those of tumor necrosis factor (TNF) inhibitors, TCZ displays certain differences. The most notable advantage of TCZ is its usefulness as a monotherapy. Additionally, TCZ is favorable in the improvement of systemic inflammatory symptoms such as anemia and fatigue. The low immunogenicity of TCZ contributes favorably to long-term drug retention. Due to frequent relapse after TCZ cessation, TCZ use should be tapered beyond remission. During TCZ therapy, C-reactive protein (CRP) is unable to recognize disease activity and the severity of infection. The most common adverse events (AEs) are infection and abnormalities in laboratory findings including dyslipidemia, neutropenia, thrombocytopenia, and abnormality of liver enzymes. TCZ obscures the symptoms of infection. Therefore, stealth infections without obvious CRP elevation can sometimes cause severe damage to patients. Lower intestinal perforation is an uncommon but serious AE in TCZ therapy. Further clinical investigations will continue to refine the IL-6 inhibitory strategy.

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“…However, cytokine IL-6 can inhibit the differentiation of T cells and impair T-cell immunity. 23 Therefore, the observed decrease in the number of T cells can be a secondary event of a cytokine storm. SARS-CoV-2 shares more than 60% sequence identity with these four cold-causing CoV's and share even more than 80% sequence identity with SARS-CoV.…”

Section: Ade Can Explain Characteristics Of Severe Covid-19mentioning

confidence: 99%

Immunoregulation with mTOR inhibitors to prevent COVID‐19 severity: A novel intervention strategy beyond vaccines and specific antiviral medicines

Zheng¹,

Liu

2020

Journal of Medical Virology

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Coronavirus disease 2019 (COVID-19) has become a major global public health concern. The mortality rate for critically ill patients is up to 60%, and, thus, reducing the disease severity and case mortality is a top priority. Currently, cytokine storms are considered as the major cause of critical illness and death due to COVID-19.After a systematical review of the literature, we propose that cross-reactive antibodies associated with antibody-dependent enhancement (ADE) may actually be the cause of cytokine storms. It would be more difficult to develop vaccines for highly pathogenic human coronaviruses (CoVs) if ADE characteristics are taken into consideration. Therefore, it is urgent to find an effective way to prevent the occurrence of severe illness as severe acute respiratory syndrome CoV-2 specific drugs or vaccines are still in development. If the activation of memory B cells can be selectively inhibited in high-risk patients at an early stage of COVID-19 to reduce the production of cross-reactive antibodies against the virus, we speculate that ADE can be circumvented and severe symptoms can be prevented. The mammalian target of rapamycin (mTOR) inhibitors satisfy such needs and it is recommended to conduct clinical trials for mTOR inhibitors in preventing the severity of COVID-19. K E Y W O R D S ADE, antibody-dependent enhancement, coronavirus, cross-reactive antibody, cytokine storm, immunity, mTOR inhibitors, rapamycin How to cite this article: Zheng Y, Li R, Liu S. Immunoregulation with mTOR inhibitors to prevent COVID-19 severity: A novel intervention strategy beyond vaccines and specific antiviral medicines.

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Immune‐suppressive effects of interleukin‐6 on T‐cell‐mediated anti‐tumor immunity

Cited by 124 publications

References 59 publications

Cytoglobin Attenuates Neuroinflammation in Lipopolysaccharide-Activated Primary Preoptic Area Cells via NF-κB Pathway Inhibition

Cytoglobin Attenuates Neuroinflammation in Lipopolysaccharide-Activated Primary Preoptic Area Cells via NF-κB Pathway Inhibition

IL-6 inhibitor for the treatment of rheumatoid arthritis: A comprehensive review

Immunoregulation with mTOR inhibitors to prevent COVID‐19 severity: A novel intervention strategy beyond vaccines and specific antiviral medicines

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