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 ac tivities and can affect a variety of target cells or systems in multiple wa ys. However, there is currently no consensus on how IL-6 directly affects t he peripheral nervous tissue. We performed histopathological and immunohist ochemical analyses to investigate the direct effects of recombinant rat IL- 6 (rrIL-6) following its intraneural injection into the sciatic nerve of ad ult Lewis rats. One day after injection, a large number of macrophages, maj or 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 a nd demyelination. On day 7, demyelination affected more than 80% of nerve f ibres. In contrast, in the sterile phosphate-buffered saline (PBS)-injected control group, lower inflammation and fewer demyelinating nerve fibres wer e observed on days 4 and 7. Thus, intraneural injection of rrIL-6 into the sciatic nerve induces high inflammation and severe demyelination. This stud y improves our understanding of the effector mechanisms underlying inflamma tion and demyelination and identifies IL-Gas an essential mediator of infla mmation and demyelination in the peripheral nervous system after local admi nistration.