Interleukin 23 in Acute Inflammatory Demyelination of the Peripheral Nerve

Abstract

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 transcriptase-polymerase 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.

Immune circuitry in the peripheral nervous system

“…In a recent study macrophages could be identified as the cellular source of interleukin-23, a proinflammatory cytokine acting on subtypes of T cells. Hu et al [59] demonstrated that this cytokine is expressed during the clinical course of EAN with expression levels at a peak prior to maximal clinical disease severity. Along this line, interleukin-23 was detectable in the cerebrospinal fluid as well as in sural nerve biopsies from patients with GBS, suggesting that this cytokine might play a critical role during the early effector phase of immune-mediated demyelination of the peripheral nerve.…”

Inflammatory neuropathies: pathology, molecular markers and targets for specific therapeutic intervention

“…In situ cellular infiltrates in AIDP have been shown to express certain proinflammatory molecules by immunohistochemistry such as costimulatory molecule CD80 by endoneurial macrophages, inducible costimulatory (ICOS) on T lymphocytes and ICOS ligand on endoneurial macrophages, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) was on endoneurial macrophages, inhibitor of kappa B (I-κB) on endoneurial macrophages and T lymphocytes, interleukin-23 p19 subunit by endoneurial macrophages, Fcγ receptors on endoneurial macrophages, and macrophage differentiation markers MRP14 and 27E10 [64,63,49,3,48,97]. Chemokine receptors CCR1, CCR2 and CCR5 on endoneurial macrophages, and CCR2, CCR4 and CXCR3 on infiltrating T lymphocytes have also been described in AIDP [66,101].…”

CD73 is expressed on invading T lymphocytes in the inflamed peripheral nerve

“…5 This study was approved by the local ethics committee. Immunohistochemical staining was performed on 10-m cryostat sections, as previously described, 5 using FITC (fluorescein isothiocyanate)-conjugated antihuman CD3, CD4, CD8, and CD68 as well as PE (phycoerythrin)-conjugated antimouse IgG antibodies (all BD Biosciences, Heidelberg, Germany).…”