Interleukin-6 cytokine: An overview of the immune regulation, immune dysregulation, and therapeutic approach

Aliyu, Mansur; Zohora, Fatema Tuz; Anka, Abubakar Umar; Ali, Kawsar; Maleknia, Shayan; Saffarioun, Mohammad; Azizi, Gholamreza

doi:10.1016/j.intimp.2022.109130

Cited by 60 publications

(34 citation statements)

References 181 publications

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“…The CRS is implicated in the immunopathogenesis of various disease complications like ARDS and multi-organ failure, including acute lung injury, acute kidney injury, and cardiac injury, even leading to death in COVID-19 patients ( Mehta Y. et al, 2020 ; Yang et al, 2020 ). The key prognosis markers are elevated serum levels of IL-6 and IFN-gamma ( Aliyu et al, 2022 ). The high mortality rate has been linked with pulmonary embolism and cerebral thromboembolism triggered by vascular disorders attributed to hyperinflammation induced by cytokine storm and multisystem failures, including respiratory failure rendered by microthrombi-induced capillary congestion in alveolar disorders ( Tanaka, 2023 ).…”

Section: Jakinibs and Covid-19mentioning

confidence: 99%

Therapeutic implications of current Janus kinase inhibitors as anti-COVID agents: A review

et al. 2023

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Severe cases of COVID-19 are characterized by hyperinflammation induced by cytokine storm, ARDS leading to multiorgan failure and death. JAK-STAT signaling has been implicated in immunopathogenesis of COVID-19 infection under different stages such as viral entry, escaping innate immunity, replication, and subsequent inflammatory processes. Prompted by this fact and prior utilization as an immunomodulatory agent for several autoimmune, allergic, and inflammatory conditions, Jakinibs have been recognized as validated small molecules targeting the rapid release of proinflammatory cytokines, primarily IL-6, and GM-CSF. Various clinical trials are under investigation to evaluate Jakinibs as potential candidates for treating COVID-19. Till date, there is only one small molecule Jakinib known as baricitinib has received FDA-approval as a standalone immunomodulatory agent in treating critical COVID-19 patients. Though various meta-analyses have confirmed and validated the safety and efficacy of Jakinibs, further studies are required to understand the elaborated pathogenesis of COVID-19, duration of Jakinib treatment, and assess the combination therapeutic strategies. In this review, we highlighted JAK-STAT signalling in the pathogenesis of COVID-19 and clinically approved Jakinibs. Moreover, this review described substantially the promising use of Jakinibs and discussed their limitations in the context of COVID-19 therapy. Hence, this review article provides a concise, yet significant insight into the therapeutic implications of Jakinibs as potential anti-COVID agents which opens up a new horizon in the treatment of COVID-19, effectively.

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Section: Jakinibs and Covid-19mentioning

confidence: 99%

Therapeutic implications of current Janus kinase inhibitors as anti-COVID agents: A review

et al. 2023

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“…In the PBMCs activation assay, YG-003D3 induced stronger IFN-g, IL-6, and TNF-a secretion compared to that induced by its parental anti-PD-1 or anti-LAG-3 antibodies. Although IL-6 is not the major cytokine secreted by T cells, some literature reports that IL-6 may be secreted by monocytes, macrophages, and dendritic cells (62)(63)(64). Therefore, it can be speculated that YG-003D3 may affect other immune cells, either directly or indirectly, and then induce the expression of IL-6.…”

Section: Discussionmentioning

confidence: 99%

PD-1/LAG-3 bispecific antibody potentiates T cell activation and increases antitumor efficacy

Shi

Zhou

Liu³

et al. 2022

Front. Immunol.

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Several clinical studies demonstrate that there exist other immune checkpoints overexpressed in some PD-1 inhibitor-resistant tumor patients. Among them, Lymphocyte-activation gene 3 (LAG-3) is one of the important immune checkpoint molecules and has been clinically demonstrated to have synergistic anti-tumor effects in combination with PD-1 antibody. In this study, we designed a novel ‘knob-in-hole’ PD-1/LAG-3 bispecific antibody (BsAb) YG-003D3. In conclusion, the BsAb maintained the similar affinity and thermal stability to the parental antibody, and the BsAb structure can be independent of each other in the process of double-target recognition, and the recognition activity will not be affected. Moreover, the BsAb can not only target PD-1 and LAG-3 on single cell simultaneously, but also bridge the two kinds of cells expressing PD-1 and LAG-3, so as to release the ‘brake system of immune checkpoints’ and activate immune cells to exert anti-tumor effects more effectively. Especially in the PBMCs activation assay, YG-003D3 induced stronger IFN-γ, IL-6, and TNF-α secretion compared to anti-PD-1 or anti-LAG-3 single drug group or even combined drug group. In the tumor killing experiment of PBMC in vitro, YG-003D3 has a better ability to activate PBMC to kill tumor cells than anti-PD-1 or anti-LAG-3 single drug group or even combined drug group, and the killing rate is as high as 20%. In a humanized PD-1/LAG-3 transgenic mouse subcutaneous tumor-bearing model, YG-003D3 showed good anti-tumor activity, even better than that of the combination group at the same molar concentration. Further studies have shown that YG-003D3 could significantly alter the proportion of immune cells in the tumor microenvironment. In particular, the proportion of CD45+, CD3+ T, CD8+ T cells in tumor tissue and the proportion of CD3+ T, CD8+ T, CD4+ T cells in peripheral blood were significantly increased. These results suggest that YG-003D3 exerts a potent antitumor effect by activating the body ‘s immune system. In summary, the BsAb YG-003D3 has good anti-tumor activity, which is expected to become a novel drug candidate for cancer immunotherapy.

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“…Unfortunately, it is challenging to predict which cytokines will be produced in which quantities, since it all depends on the uniqueness of one's immune response, but a common denominator that must be addressed in this treatment proposal is the management of IL-6 as well as the blockage of PD-L1. IL-6 is a proinflammatory cytokine with pleiotropic biological activities, including the induction and maintenance of B cell modulation and Th17 cell differentiation, among other actions related to acute inflammation, such as the induction of acute-phase reactants synthesis by the liver [22]. IL-6 is known to elicit the most dangerous effects of the COVID-19 cytokine storm, as well as to dampen the recruitment and development of lymphocytes; therefore its blockade was suggested as a possible therapy, especially for patients with a severe infection [23].…”

Section: Proposed Mechanisms For Sars-cov-2 As An Oncolytic Virusmentioning

confidence: 99%

SARS-CoV-2 as an Oncolytic Virus Following Reactivation of the Immune System: A Review

Bounassar-Filho

Boeckler-Troncoso

Cajigas-Gonzalez

et al. 2023

IJMS

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The effects SARS-CoV-2 inflicts on human physiology, especially in patients who developed COVID-19, can range from flu-like symptoms to death, and although many lives have been lost during the pandemic, others have faced the resolution of aggressive neoplasms that were once considered with a poor prognosis following traditional treatments. The purpose of this review was to analyze several fortunate case reports and their associated biomolecular pathways to further explore new avenues that might provide oncological treatments in the future of medicine. We included papers that discussed cases in which patients affected by COVID-19 suffered beneficial changes in their cancer status. Multiple mechanisms which elicited a reactivation of the host’s immune system included cross-reactivity with viral antigens and downregulation of neoplastic cells. We were able to identify important cases presenting the resolution/remission of different aggressive neoplasms, for which, most of the time, standard-of-care treatments offered little to no possibility towards a cure. The intricacy of the defense mechanisms humans have adopted against cancer cells through the millennia are still not well understood, but SARS-CoV-2 has demonstrated that the same ruinous cytokine storm which has taken so many lives can paradoxically be the answer we have been looking for to recalibrate the immunological system to retarget and vanquish malignancies.

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Interleukin-6 cytokine: An overview of the immune regulation, immune dysregulation, and therapeutic approach

Cited by 60 publications

References 181 publications

Therapeutic implications of current Janus kinase inhibitors as anti-COVID agents: A review

Therapeutic implications of current Janus kinase inhibitors as anti-COVID agents: A review

PD-1/LAG-3 bispecific antibody potentiates T cell activation and increases antitumor efficacy

SARS-CoV-2 as an Oncolytic Virus Following Reactivation of the Immune System: A Review

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