scholarly journals Leveraging genetic data to investigate the effects of interleukin‐6 receptor signalling on levels of 40 circulating cytokines

2021 ◽  
Author(s):  
Rezbieara P. Rahman ◽  
Lauren McEwan ◽  
David K. Ryan ◽  
Dipender Gill
Keyword(s):  
Interleukin 6 ◽  
Genetic Data ◽  
Receptor Signalling ◽  
Interleukin 6 Receptor ◽  
Circulating Cytokines

scholarly journals Leveraging genetic data to investigate the effects of interleukin-6 receptor signalling on levels of 40 circulating cytokines.

2021 ◽  
Author(s):  
Rezbieara Rahman ◽  
Lauren McEwan ◽  
David Ryan ◽  
Dipender Gill
Keyword(s):  
Interleukin 6 ◽  
Inflammatory Diseases ◽  
Association Studies ◽  
Genome Wide Association Studies ◽  
Compensatory Mechanisms ◽  
Genome Wide ◽  
Level Data ◽  
Interleukin 6 Receptor ◽  
Study Support ◽  
Circulating Cytokines

Abstract Interleukin 6 (IL-6) is a circulating cytokine that is implicated in a range of inflammatory diseases. However, the broad effects of IL-6 receptor (IL-6R) signalling on other circulating cytokines is not known. Using summary-level data from genome-wide association studies, we leveraged genetic variants that proxy IL-6R signalling in two-sample Mendelian randomization analyses to investigate effects on levels of 40 circulating cytokines. Increased genetically proxied IL-6R signalling was associated with reduced levels of 10 circulating interleukins, chemokines, and growth factors. The findings from this study support feedback effects of IL-6R signalling on reducing levels of a range of circulating cytokines and identify compensatory mechanisms that may be modulating its inflammatory effects. These results provide novel insight into the mechanisms by which IL-6R signalling may be contributing to inflammatory and autoimmune diseases.

The effect of tocilizumab - an interleukin-6 receptor antagonist - on lipid levels in rheumatoid arthritis

2017 ◽  
Author(s):  
Ifigenia Kostoglou-Athanassiou ◽  
Lambros Athanassiou ◽  
Aikaterini Tzanavari ◽  
Charoula Katsavouni ◽  
Markos Kostopoulos ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Receptor Antagonist ◽  
Interleukin 6 ◽  
Lipid Levels ◽  
Interleukin 6 Receptor

A synthetic corticosteroid, dexamethasone regulates generation of soluble form of interleukin-6 receptor of human lymphocytes, in vitro

2002 ◽  
Vol 53 (3) ◽  
pp. 307-315 ◽  
Author(s):  
Anna Polgár ◽  
Márta Brózik ◽  
Sára Tóth ◽  
Marcsilla Holub ◽  
A. Falus
Keyword(s):  
Interleukin 6 ◽  
Human Lymphocytes ◽  
Soluble Form ◽  
Interleukin 6 Receptor

Decidua Is a Possible Source of Serum Mouse Soluble Interleukin-6 Receptor (msIL-6R): Gestational Profile of Serum msIL-6R Concentration

1994 ◽  
Vol 205 (2) ◽  
pp. 998-1003 ◽  
Author(s):  
T. Maeda ◽  
M. Yamaguchi ◽  
T. Taga ◽  
T. Kishimoto ◽  
K. Wada ◽  
...  
Keyword(s):  
Interleukin 6 ◽  
Interleukin 6 Receptor

657 Interleukin-6 receptor blockade for management of immune checkpoint inhibitor related adverse events in patients with melanoma

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A694-A694
Author(s):  
Chantal Saberian ◽  
Faisal Fa’ak ◽  
Jean Tayar ◽  
Maryam Buni ◽  
Sang Kim ◽  
...  
Keyword(s):  
Adverse Events ◽  
Disease Activity ◽  
Median Time ◽  
Interleukin 6 ◽  
Immune Checkpoint ◽  
Activity Index ◽  
Critical Role ◽  
Cancer Center ◽  
Interleukin 6 Receptor ◽  
Md Anderson

BackgroundManagement of certain immune mediated adverse events (irAEs) can be challenging and may require prolonged/chronic immune suppression with corticosteroids or other immunosuppressant which could compromise and even reverse the efficacy of immune checkpoint inhibitors (ICI). While the exact immunobiology of irAEs is not fully understood there is enough evidence that IL-6 induced Th-17 that may play critical role in the pathogenesis. Herein, we describe our clinical experience using interleukin-6 receptor (IL-6R) blockade in management of irAEs in melanoma patients.MethodsWe searched MD Anderson databases to identify cancer patients who had received ICIs between January 2004 and March 2020. Of 11,391 ICI-treated patients, 21 patients with melanoma who received IL-6R blockade after ICI infusion were identified and their medical records were reviewed.ResultsMedian age was 61 years (41–82), 52% were females, 90% received anti-programmed cell death-1 antibodies. Fourteen patients (67%) had de novo onset irAEs (11 had arthritis, and 1 each with polymyalgia rheumatica, oral mucositis, and CNS vasculitis), and 7 patients (33%) had flare of their pre-existing autoimmune diseases (5 had had rheumatoid arthritis, and 1 each with myasthenia gravis and Crohn’s disease). Median time from ICI initiation to irAEs was 91 days (range, 1–496) and to initiation of IL-6R blockade was 6.6 months (range, 0.6–24.3). Median number of IL-6R blockade was 12 (range, 1–35), and 16 patients (76%) were concomitantly receiving corticosteroids of median dose of 10 mg (range, 5–20 mg). Of the 21 patients, irAEs improved in 14 (67%) (95% CI: 46%-87%). Of 13 evaluable patients with arthritis, 11 (85%) achieved remission or minimal disease activity as defined by the clinical disease activity index. Median time from initiation of IL-6R blockade till improvement of irAEs was 2.9 months (range, 1.5–36.9). Nineteen patients tolerated well IL-6R blockade, while two patients stopped treatment due to abdominal pain and sinus tachycardia. The median CRP levels at irAEs was 84 mg/L (0.6–187) and decreased to 1.9 mg/L (0.56–12) at 10 weeks after initiation of IL-6R blockade (P=0.02). Of the 17 evaluable patients, the overall tumor response rate by RECIST-1.1 criteria was similar before and after IL-6R blockade initiation (41% vs. 53%).ConclusionsOur data demonstrated that IL-6R blockade could be an effective therapy for irAEs management without dampening the efficacy of ICIs. Prospective clinical trials with longitudinal blood, tumor, and inflamed tissue biopsies are planned to accurately validate these findings and better study the immunobiology of irAEs.Ethics ApprovalThe study was approved by The University of Texas MD Anderson Cancer Center intuition’s Ethics Board, approval number PA19-0089

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