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Association between circulating inflammatory cytokine levels and the risk of polymyositis: A bidirectional Mendelian

Jiang Shao1,2, Jinjiao Xie1,2, Xiaoli Zheng3

  • 1Department of Rheumatology and Immunology, The First People's Hospital of Neijiang, Neijiang, China.

International Reviews of Immunology
|March 30, 2026
PubMed
Abstract

Insights

Mendelian randomization revealed that lower granulocyte colony-stimulating factor (GCSF) levels increase polymyositis (PM) risk. Polymyositis also impacts interleukin-13, interleukin-7, and IL-1 receptor antagonist levels, suggesting potential therapeutic targets.

Area of Science:

  • Immunology
  • Genetics
  • Epidemiology

Background:

  • Investigating the link between inflammatory cytokines and polymyositis (PM) is complex due to observational study limitations.
  • Mendelian randomization (MR) offers a robust approach to infer causal relationships.

Purpose of the Study:

  • To assess the causal effect of 41 circulating inflammatory cytokines on polymyositis (PM) risk using a two-sample Mendelian randomization design.
  • To identify potential biomarkers for PM pathogenesis and therapeutic intervention.

Main Methods:

  • Utilized genome-wide association study (GWAS) data from European ancestry individuals for inflammatory modulators (n=8,186) and PM (n=213,264).
  • Employed inverse variance-weighted (IVW) as the primary MR analysis method.
  • Conducted sensitivity analyses using MR-Egger, weighted-median, MR-PRESSO, and Cochran's Q tests to ensure robustness.

Main Results:

  • Decreased granulocyte colony-stimulating factor (GCSF) levels were causally associated with increased PM risk (OR=0.31).
  • Increased circulating levels of interleukin-13 (IL-13) and interleukin-7 (IL-7) were associated with PM risk (OR=1.03 for both).
  • Decreased levels of IL-1 receptor antagonist (IL-1RA) were associated with PM risk (OR=0.97).

Conclusions:

  • Granulocyte colony-stimulating factor (GCSF) appears to play a significant role in polymyositis (PM) pathogenesis.
  • PM influences the circulating levels of IL-13, IL-7, and IL-1RA.
  • These cytokines represent potential targets for future PM prevention and treatment strategies.
Keywords:
Circulating inflammatory factorsGWASMendelian randomizationpolymyositissingle nucleotide polymorphisms

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