How IL-6 Signaling Works

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IL-6 signals through 2 distinct mechanisms1-7

  • Interleukin-6 (IL-6) can signal through membrane-bound receptors (classical or cis-signaling)

  • IL-6 can also signal through soluble forms of its receptors (trans-signaling)

  • These 2 distinct signaling mechanisms allow IL-6 to interact with cells that express the IL-6 membrane-bound receptor (mIL-6R), as well as with cells that do not

IL-6 signals through classical signaling and trans-signaling1-7

The presence of both membrane-bound and soluble receptors gives IL-6 an expanded range of biological activities, allowing it to interact with a wide array of cells and tissues.1,7,9,14-19

Adapted from Choy 2004.

In rheumatoid arthritis (RA), multiple cytokines, including IL-6, TNF-α, IL-1, and IL-17, trigger pro-inflammatory responses through membrane-bound receptors1,7,20-22

  • Receptors for tumor necrosis factor-α (TNF-α) or IL-1 are also expressed as membrane-bound and soluble forms20,21

  • Inflammatory signaling for TNF-α and IL-1 is mediated by the membrane-bound form of the receptor20,21

Cytokine signaling pathways in RA1-7,23

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