IL-6/STAT3 growth signalling induced by exercise conditioning promotes regeneration of injured rat sciatic nerve: return to an old cytokine

The effects of interleukin-6 (IL-6), a growth promoting myokine through signal transduction, and activator of transcription 3 (STAT3), as a growth promoting signal, in peripheral nerve injury (PNI) are still unclear, including whether exercise pre- and/or post-conditioning are useful in nerve regeneration. Four groups were included in the study: sham for sciatic nerve injury (control), sciatic nerve injury group (SNI), exercise post-conditioning (SNI+Ex) and exercise pre- and post-conditioning (Ex+SNI+Ex). IL-6 levels were measured in serum, muscle, nerve and its surrounding fascia. Elevated levels of IL-6 in serum, nerve, muscle and fascia revealed that IL-6 induced in nerve by exercise were: (1) local nerve tissue expression; (2) serum diffused as a myokine from contracting muscle; and (3) diffused for surrounding peri-tendinous region. Evaluation of nerve functions shows that, exercise post-conditioning significantly improved (P\u3c0.05) nerve functions in the form of nerve conduction velocity (NCV) (19.21±4.30 vs 10.96±3.08 m/s), compound muscle action potential amplitude (CMAP) (0.26±0.06 vs 0.18±0.06 mv), histologic improvement in myelination% (35.63±3.92 vs 21.13±4.26) and number of nerve fibres (181.75±9.6 vs 145.75±9.67). However, combined pre- and post-conditioning improved NCV (26.95±2.41 vs 19.21±4.30 m/s) and % myelination (43.50±3.16 vs 35.63±3.92) (P\u3c0.05) when compared with the exercise post-conditioning group. In conclusion, IL-6 induced by exercise is valuable in nerve regeneration. The IL-6/STAT3 growth pathway could be a treatment target in clinical trials in PNI conditions