Rheumatology

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Interleukin 17 (IL-17) increases the expression of toll-like receptor-2, 4, and 9 by increasing IL-1β and IL-6 production in autoimmune arthritis
Journal of Rheumatology, 04/08/09

Lee JH et al. – Data support the observation that interleukin 17 (IL-17) aggravates joint inflammation and destruction, and increases the synovial expression of Toll-like receptor (TLR)-2, 4, and 9 by increasing IL-1β and IL-6, implying that this pathway is involved in aggravation of arthritis.

• Aim was to examine the effect of IL-17 on the expression of TLR- 2, 4, and 9 in collagen-induced arthritis (CIA) in mice
• On Days 28 and 32 after induction of CIA, PBS or IL-17 was injected into both knee joints
• On Day 35, the severity of knee joint arthritis, synovial inflammation, and bone destruction was measured
• Synovial expression of TLR-2, 4, 9, IL-17, IL-1β, TNF-α, and IL-6 was determined by RT-PCR and IHC
• Synoviocytes of CIA mice were cultured with IL-17 and with neutralizing Abs to cytokine
• Expression of TLR-2, 4, 9, IL-1β, TNF-α, and IL-6 was determined by RT-PCR

• In CIA mice, higher expression was seen in IL-17 and PBS group vs normal DBA1 mice of:
  • knee arthritis scores, synovial inflammation, bone destruction scores
  • and expression of synovial TLR-2, 4, and 9, IL-17, IL-1β, TNF-α, and IL-6
• These variables were also higher in the IL-17 group vs PBS group
• In CIA synoviocytes, IL-17 increased the expression of TLR-2, 4, and 9
• This effect was alleviated by neutralizing Abs to IL-17, IL-1β, and IL-6

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