Question: 

The cytokine IL-17 has recently been shown to play a role in rheumatoid arthritis where it contributes to the inflammatory process and the destruction of cartilage. Here we tested whether IL-17 has also the potency to induce nociception in a normal joint.

Method: 

Healthy adult WISTAR rats were anesthetized with sodium thiopentone (100 mg/kg, i.p.). The knee joint was mechanically stimulated by innocuous (20 mNm) or noxious (40 mNm) rotations of the lower leg against the fastened femoral bone for 15 sec each and nerve action potentials were counted. Nerve fibers were classified as C- or as Ad-fibers by their conduction velocity (<1.4 m/s or <10 m/s, respectively). Hundred ml of the compounds were injected into the joint cleft.

Results: 

C-fiber responses were significantly enhanced by 100 ng IL-17 (net increase to innocuous stimulation 61.2±41.9 APs/15 sec, to noxious stimulation 142.2±51.7 APs/15 sec within three hours; mean±SEM, respectively) but not by 50 ng IL-17 or by 500 ng IL-17. The latter dose even deleted action potential firing of C-fibers. Ad-fiber responses were only enhanced by 500 ng IL-17 (net increase to innocuous stimulation 145.7±60.1 APs/15 sec, to noxious stimulation 151.2±47.3 APs/15 sec within three hours). Neither the blockade of the TNF-a nor of the IL-6 signaling pathways inhibited the sensitizing effect of 100 ng IL-17 to C-fibers. Adding TNF-a to IL-17 did not potentiate the sensitizing effect.

Conclusions: 

Thus we conclude that IL-17 is a pronociceptive cytokine that exerts alone a sensitizing effect on slowly conducting C-fibers thereby contributing to inflammatory joint pain.