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Interleukin 23 in Acute Inflammatory Demyelination of the Peripheral Nerve
Wei Hu, MD;
Thomas Dehmel, PhD;
Jaana Pirhonen, PhD;
Hans-Peter Hartung, MD;
Bernd C. Kieseier, MD
Arch Neurol. 2006;63:858-864.
Background Interleukin (IL) 23, a newly identified heterodimeric proinflammatory cytokine and a novel IL-12 family member comprising the p40 subunit of IL-12 but a different p19 subunit, has been reported to preferentially act on memory T cells and play an important role during cellular immune responses. Recent evidence suggests that IL-23 rather than IL-12 is critically involved in the pathogenesis of various immune-mediated disorders.
Objective To determine the role of IL-23p19 during the course of acute immune-mediated demyelinating diseases of the peripheral nervous system.
Design The sequential RNA expression of IL-23p19 in sciatic nerves from rats with experimental autoimmune neuritis, an animal model of the human Guillain-Barré syndrome (GBS), was analyzed by semiquantitative reverse transcriptasepolymerase chain reaction. Expression and distribution patterns of IL-23p19 protein were studied in sural nerve biopsies and cerebrospinal fluid samples from 5 patients with classical Guillain-Barré syndrome and 5 controls with noninflammatory neuropathies using immunohistochemistry and immunoblotting, respectively.
Results We found IL-23p19 RNA to be up-regulated prior to the onset of first clinical symptoms with peak expression levels preceding maximum disease severity during experimental autoimmune neuritis. In patients, IL-23p19 protein was detectable in cerebrospinal fluid samples from patients with Guillain-Barré syndrome, and endoneurial macrophages were identified as the cellular source of IL-23p19 in sural nerve biopsies.
Conclusion Our present data indicate that IL-23 may play an important role during the early effector phase in immune-mediated demyelination of the peripheral nerve.
Author Affiliations: Department of Neurology (Drs Hu, Dehmel, Hartung, and Kieseier), Research Group for Clinical and Experimental Neuroimmunology, Heinrich-Heine-University, Düsseldorf, Germany; and Department of Microbiology (Dr Pirhonen), National Public Health Institute, Helsinki, Finland.
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