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"39 The IL-1R antagonist anakinra was approved for severe COVID-19 by the European Medicines Agency39 while the United States Food and Drug Administration had issued an Emergency Use Authorization (EUA) for the emergency use of anakinra for hospitalized adults with COVID-19 pneumonia requiring supplemental oxygen who were at risk of progressing to severe respiratory failure and likely to have an elevated plasma soluble urokinase plasminogen activator receptor.40 Although this suggests the pathogenetic role of IL-1β in COVID-19, our findings imply that IL-1β and IL-1R1 could serve as molecules that mediate an interaction between myeloid cells, including monocytes and macrophages, and CD4 Th cells for the development of adaptive immune responses to SARS-CoV-2."
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"Furthermore, patients with grade 3 or 4 CRS should be transferred to intensive care for continuous monitoring, management of arrhythmias and circulatory shock, and provision of noninvasive positive pressure or mechanical ventilation as needed.Preclinical studies have demonstrated the utility of the IL-1R antagonist anakinra alone and in combination with tocilizumab in the management of CAR T-cell therapy–associated CRS.22 Case reports have also demonstrated its utility in patients with multiple myeloma receiving anti-BCMA CAR T-cell therapy."
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"IL-1R antagonist anakinra, which is FDA-approved for the treatment of rheumatoid arthritis and neonatal-onset multisystem inflammatory disease, has also been under trial for multiple cancers, and outcomes are awaited.Siltuximab (anti-IL-6 antibody) showed promising preclinical results in the xenograft cholangiocarcinoma model [110] but did not achieve an impressive outcome in multiple myeloma clinical trials in combination with bortezomib [111]."
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"Zhou et al demonstrated that suppressing IL-1 signalling with the IL1β-specific blocking antibody Canakinumab, or the IL1R1 antagonist Anakinra, could effectively eradicate breast cancer-induced bone metastasis.82 Canakinumab has shown effects in reducing lung cancer incidence in a clinical trial,83 84 and a phase I clinical trial involving Anakinra for rectal cancer has been initiated.85 Moreover, it has been revealed that IL6 inhibitors, such as siltuximab (anti-IL6 mAb) and tocilizumab (an anti-IL6R mAb), are effective in multiple clinical cancer treatments, including myeloma, metastatic renal cell carcinoma and prostate cancer.8689 Alternatively, Mac-1/ICAM1 inhibitors A-20580481 and Vcam1/VLA-4 antagonist natalizumab may be applied to disrupt the formation of CTC-neutrophil clusters.90
CTC-platelet cluster."
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"Because autocrine IL-1R signaling is a critical component that drives the canonical NF-kb cascade in PDAC, the combination of the IL-1R antagonist Anakinra with nab-paclitaxel, gemcitabine, and cisplatin has been opened in a pilot clinical trial for patients with resectable or potentially resectable PDAC (NCT02550327)."
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"Interestingly, in CAFs with already a basal activation of the NFκB pathway, the addition of the IL1R1 antagonist Anakinra to untreated CAFs reduced the nuclear presence of p65 and thereby the activation of the NFκB pathway, supporting the existence of an IL-1-driven autocrine loop in CAFs, which potentially helps maintain the pro-tumorigenicity of these cells (Supplementary Fig. 4h)."
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"Cumulatively, these results suggest that the absence of Il1r1 delays premalignant disease progression and mortality observed in Tet2-KO mice.We next examined whether treatment with an FDA-approved IL1R1 antagonist anakinra impedes Tet2-KO myeloid expansion in a competitive transplantation model (Fig. 5e)."
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"The proinflammatory cytokine IL1β also might contribute to TAN accumulation, polarization, and survival in the TME.109 Here again, combining the anti-IL1β antibody canakinumab or the IL1R antagonist anakinra with ICIs in clinical trials might affect both IL1β-mediated cancer cell proliferation and TANs (table 1)."
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"We have demonstrated that the accumulation of amyloid triggers lysosomal enlargement and reduces autophagosome fusion with lysosomes, thus impairing the autophagy flux, which in turn may exacerbate amyloid deposition in a vicious cycle.7 35 Moreover, amyloids trigger inflammatory cascades in MPS by triggering microglia and astrocyte activation, leading to a destructive neuroinflammatory environment.27 43 Of note, a recent clinical trial testing the anti-inflammatory IL-1R antagonist anakinra has shown significant improvement in multiple neurobehavioral domains of patients with MPS-III.55 Therefore, amyloid storage is a key factor underlying multiple deleterious mechanisms downstream of the primary enzyme defect and GAG storage in different neuronopathic MPSs.To date, targeting the secondary storage of toxic amyloidogenic proteins has only been explored for the treatment of neuronopathic MPS by our team."
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"Finally, the authors define the contributions of IL-6 and PDGF to the PH phenotype in the myelomonocytic Regnase-1 deficient mice by showing that treatment with either an IL-6 neutralizing antibody (MR16–1) or imatinib, a multi-kinase inhibitor of PDGFRβ, both partially attenuated the PH and vascular obliterative phenotype, while IL1R antagonist anakinra did not exert a significant impact."
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"The IL-1R antagonist anakinra, IL-17 inhibitors, and pegylated interferon-λ1 are testable Food and Drug Administration-approved drugs predicted from this study to therapeutically mitigate the elevated systemic inflammatory response and associated cardiac dysfunction consequent to surgical repair of complex neonatal CHD."
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"Our ongoing research aims to bridge this gap, enhancing the relevance and applicability of our murine model system to human BCC.Overall, the identification of TREM1+ myeloid-derived IL1 and OSM as sufficient to induce BIT and resistance generates a unique therapeutic opportunity to target BIT using currently available agents such as IL1R antagonist Anakinra or JAK inhibitors."
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"Although the functional role of IL-1 in central COVID-19-related neuropathologies remains unclear, improved clinical outcomes alongside reduced IL-6 and CRP levels after early treatment of patients with COVID-19 with the IL-1R1 antagonist anakinra suggest that this regimen might also be considered to alleviate symptoms in Neuro-COVID."
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"Since blockade of IL-1R by anakinra reduced leukocyte levels in both HPV-positive and HPV-negative OPSCC in vitro, it could be argued that this antagonist may be effective for both types of tumour, however, the increased numbers of leukocytes recruited to HPV-negative OPSCC suggests that the treatment would be most effective for this cancer type."
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"In some experiments, IL-1R antagonist Anakinra (100 ng/mL), anti-IL-1β mAb (150 ng/mL), anti-TNF-R1 (50 ng/mL) plus anti-TNF-R2 mAbs (50 ng/mL), STAT1 phosphorylation inhibitor SU6656 (150 µM), or IRF1 expression inhibitor cyanidin 3-O-glucoside chloride (C3G, 300 µM) were added to investigate the signaling pathways that engaged in the PTA-induced Th9 cells differentiation.For in vitro human Th9 cell polarization, the peripheral blood mononuclear cells (PBMCs) were isolated from NSCLC patients using 1×Ficoll and further purified by flow cytometry with the MojoSort Human CD4 T Cell Isolation Kit (BioLegend)."
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"Treatment of animals having had tibia fracture and cast immobilization with IL-1R antagonist anakinra reduces not only the CRPS-like nociceptive sensitization, but also levels of the pro-nociceptive mediators IL-6, tumor necrosis factor α and nerve growth factor in hindpaw skin (12)."
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"In addition, the development of drugs such as the IL-1R antagonist anakinra (Kineret®), rionacept (Regeneron®; IL-1 trap), and canakinomab (Ilaris®; anti-IL-1β antibody) also suggests that blocking IL-1β signaling may be a potential complementary therapy for allergic airway inflammation [82, 83]."
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"A well-characterized example of a complete self-regulated inflammatory pathway is the interleukin-1 (IL-1) system comprising the agonist cytokines IL-1α and IL-1β, and their receptor IL-1R1 (IL-1 receptor type I), which is inhibited by the IL-1 receptor antagonist IL-1Ra. xref A related system involves the three IL-36 cytokines IL-36α, IL-36β and IL-36γ, which are neutralized when the IL-36Ra binds the IL-36 receptor IL-1RL2 (also known as IL-36R)."