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.
Deretzi
G
G
Department of Clinical Neuroscience, Karolinska Institute, Huddinge University Hospital, Stockholm, Sweden.
Pelidou
S H
SH
Zou
L P
LP
Quiding
C
C
Zhu
J
J
D000818:Animals; D003711:Demyelinating Diseases / Q000276:immunology / Q000473:pathology; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D015850:Interleukin-6 / Q000276:immunology / Q000633:toxicity*; D008264:Macrophages / Q000276:immunology; D008297:Male; D009443:Neuritis / Q000276:immunology / Q000473:pathology; D010523:Peripheral Nervous System Diseases / Q000276:immunology* / Q000473:pathology; D051381:Rats; D011917:Rats, Inbred Lew; D011994:Recombinant Proteins / Q000276:immunology / Q000633:toxicity; D012584:Sciatic Nerve / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology
D000949:Histocompatibility Antigens Class II; D015850:Interleukin-6; D011994:Recombinant Proteins