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Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
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Zinc suppresses Stat3-driven IL-6 production in primary mouse adipocytes.

Hak Chung1,2, John Eom1,2, Michelle Sma Damen1,2

  • 1Division of Immunobiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States.

Frontiers in Immunology
|February 25, 2026
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Summary

Zinc (Zn) was found to inhibit inflammatory IL-6 production in adipocytes, a key non-immune cell type. This discovery suggests a potential role for zinc in managing chronic diseases linked to adipocyte inflammation.

Keywords:
adipose tissuecytokinesimmunitymetalsobesitypyrithione

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Area of Science:

  • Immunology
  • Cell Biology
  • Metabolic Diseases

Background:

  • Uncontrolled inflammatory cytokine production drives chronic disease pathogenesis.
  • Zinc (Zn) modulates immune cell inflammatory responses, but its effect on non-immune cells is unclear.
  • Adipocytes contribute to disease by activating inflammatory pathways and secreting cytokines.

Purpose of the Study:

  • To investigate the impact of zinc on adipocyte inflammatory activity.
  • To determine if zinc can regulate IL-6 production in adipocytes.

Main Methods:

  • Primary mouse adipocytes were treated with zinc pyrithione.
  • Toll-like receptor ligand-driven IL-6 production was measured.
  • Stat3 signaling pathway activation and gene expression were analyzed.

Main Results:

  • Zinc pyrithione treatment restricted toll-like receptor ligand-driven IL-6 production in adipocytes.
  • Zinc suppressed Stat3 signaling, breaking a positive feedback loop that amplifies IL-6 production.
  • Expression of IL-6 and its receptor genes (Il6st, Il6ra) was reduced by zinc treatment.

Conclusions:

  • Zinc exerts a novel inhibitory effect on IL-6 production in adipocytes.
  • Zinc may play a role in regulating adipocyte-associated chronic inflammation and disease pathogenesis.