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Dysregulated IL-6 pathway activity in idiopathic inflammatory myopathies
Anja Srpčič1,2, Felicita Urzi3, Manca Ogrič1
1Department of Rheumatology, University Medical Centre Ljubljana, Ljubljana, Slovenia.
Arthritis Research & Therapy
|July 21, 2026
Summary
Idiopathic inflammatory myopathies (IIM) show increased interleukin-6 (IL-6) pathway activity, driven by a complex cytokine environment rather than IL-6 levels alone. Reduced anti-IL-6 autoantibodies may influence IL-6 bioactivity in IIM.
Area of Science:
- Immunology
- Molecular Biology
- Rheumatology
Background:
- Idiopathic inflammatory myopathies (IIM) are autoimmune diseases affecting muscles.
- The interleukin-6 (IL-6) pathway is implicated in inflammation and autoimmune conditions.
- Understanding IL-6 signalling in IIM is crucial for developing targeted therapies.
Purpose of the Study:
- To characterize IL-6 pathway activity in IIM.
- To investigate the roles of circulating IL-6, soluble IL-6 receptor (sIL-6R), and anti-IL-6 autoantibodies in IIM.
- To correlate IL-6 pathway activity with clinical parameters like muscle strength.
Main Methods:
- Transcriptomic analysis of skeletal muscle from IIM patients and controls.
- ELISA measurement of IL-6, sIL-6R, and anti-IL-6 autoantibodies in serum.
- Reporter gene assay (RGA) to quantify serum IL-6 signalling capacity.
Main Results:
- IL-6/JAK/STAT3 signalling was enriched in IIM muscle tissue.
- Serum IL-6 levels were elevated in IIM, while sIL-6R levels were similar to controls.
- IIM serum induced significantly higher IL-6 signalling in RGAs, independent of IL-6 levels, and this was linked to reduced anti-IL-6 autoantibodies.
Conclusions:
- IIM exhibits heightened systemic IL-6 pathway activity due to a dysregulated cytokine milieu.
- Reduced levels of neutralizing anti-IL-6 autoantibodies may contribute to IL-6 bioactivity in IIM.
- Targeting the IL-6 pathway could be a therapeutic strategy for IIM.
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