Local effects of recombinant rat interleukin-6 on the peripheral nervous system

Interleukin-6 (IL-6) is a multifunctional cytokine with a broad range of activities and can affect a variety of target cells or systems in multiple ways. However, there is currently no consensus on how IL-6 directly affects the peripheral nervous tissue. We performed histopathological and immunohistochemical analyses to investigate the direct effects of recombinant rat IL-6 (rrIL-6) following its intraneural injection into the sciatic nerve of adult Lewis rats. One day after injection, a large number of macrophages, major histocompatibility complex (MHC) class II positive cells, and CD4+ and CD8+ T cells appeared within the perineurium and endoneurium. From day 4 to day 7 after injection, we observed a gradual increase of inflammation and demyelination. On day 7, demyelination affected more than 80% of nerve fibres. In contrast, in the sterile phosphate-buffered saline (PBS)-injected control group, lower inflammation and fewer demyelinating nerve fibres were observed on days 4 and 7. Thus, intraneural injection of rrIL-6 into the sciatic nerve induces high inflammation and severe demyelination. This study improves our understanding of the effector mechanisms underlying inflammation and demyelination and identifies IL-6 as an essential mediator of inflammation and demyelination in the peripheral nervous system after local administration.