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Cytokines in sural nerve biopsies from inflammatory and non-inflammatory neuropathies

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Abstract

Proinflammatory cytokines are supposed to play a major role in the pathophysiology of vasculitis and in the development of neuropathic pain. Here we studied the cytokine expression in sural nerve biopsy specimens from patients with vasculitic and other inflammatory and non-inflammatory neuropathies, and investigated whether an increased cytokine expression was correlated with the presence of neuropathic pain. We used immunohistochemistry including double labeling and morphometry to localize and quantify the expression of interleukin-1 beta (IL-1β), IL-6, and tumor necrosis factor-α (TNF) in sural nerve biopsy samples of 41 patients with vasculitic neuropathy (VANP), chronic inflammatory demyelinating neuropathy (CIDP), non-inflammatory chronic axonal neuropathy (CANP), and 3 controls. Overall cytokine immunoreactivity was highest in VANP, less strong in CIDP and lowest in CANP. Cytokine immunoreactivity was directly correlated with the degree of axonal degeneration, endoneurial macrophages and epineurial T cells. In VANP and CANP, a higher cytokine content was associated with neuropathic pain.

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References

  1. Ad Hoc Subcommittee of the American Academy of Neurology AIDS Task Force (1991) Research criteria for diagnosis of chronic inflammatory demyelinating polyneuropathy (CIDP).Neurology 41:617–618

    PubMed  Google Scholar 

  2. Collins MP, Mendell JR, Periquet MI, Sahenk Z, Amato AA, Gronseth GS, Barohn RJ, Jackson CE, Kissel JT (2000) Superficial peroneal nerve/peroneus brevis muscle biopsy in vasculitic neuropathy. Neurology 55:636–643

    CAS  PubMed  Google Scholar 

  3. Dyck PJ, Benstead TJ, Conn DL, Stevens JC, Windebank AJ, Low PA (1987) Nonsystemic vasculitic neuropathy. Brain 110:843–854

    PubMed  Google Scholar 

  4. Empl M, Renaud S, Erne B, Fuhr P, Straube A, Schaeren-Wiemers N, Steck AJ (2001) TNF-alpha expression in painful and nonpainful neuropathies. Neurology 56:1371–1377

    CAS  PubMed  Google Scholar 

  5. Exley AR, Smith N, Winer JB (1994) Tumour necrosis factor-alpha and other cytokines in Guillain-Barré syndrome. J Neurol Neurosurg Psychiatry 57:1118–1120

    CAS  PubMed  Google Scholar 

  6. Flipo RM, Cardon T, Copin MC, Vandecandelaere M, Duquesnoy B, Janin A (1997) ICAM-1, E-selectin, and TNF alpha expression in labial salivary glands of patients with rheumatoid vasculitis. Ann Rheum Dis 56:41–44

    CAS  PubMed  Google Scholar 

  7. Ito Y, Yamamoto M, Mitsuma N, Li M, Hattori N, Sobue G (2001) Expression of mRNAs for ciliary neurotrophic factor (CNTF), leukemia inhibitory factor (LIF), interleukin-6 (IL-6), and their receptors (CNTFR alpha, LIFR beta, IL-6R alpha, and gp130) in human peripheral neuropathies. Neurochem Res 26:51–58

    Article  CAS  PubMed  Google Scholar 

  8. Maimone D, Annunziata P, Simone IL, Livrea P, Guazzi GC (1993) Interleukin-6 levels in the cerebrospinal fluid and serum of patients with Guillain-Barré syndrome and chronic inflammatory demyelinating polyradiculoneuropathy. J Neuroimmunol 47:55–61

    CAS  PubMed  Google Scholar 

  9. Mathey EK, Pollard JD, Armati PJ (1999) TNF alpha, IFN gamma and IL-2 mRNA expression in CIDP sural nerve biopsies. J Neurol Sci 163:47–52

    Article  CAS  PubMed  Google Scholar 

  10. Murwani R, Armati P (1998) Peripheral nerve fibroblasts as a source of IL-6, TNFalpha and IL-1 and their modulation by IFNgamma. J Neurol Sci 161:99–109

    Article  CAS  PubMed  Google Scholar 

  11. Noris M, Daina E, Gamba S, Bonazzola S, Remuzzi G (1999) Interleukin-6 and RANTES in Takayasu arteritis: a guide for therapeutic decisions? Circulation 100:55–60

    CAS  PubMed  Google Scholar 

  12. Oka N, Akiguchi I, Kawasaki T, Mizutani K, Satoi H, Kimura J (1998) Tumor necrosis factor-alpha in peripheral nerve lesions. Acta Neuropathol 95:57–62

    Article  CAS  PubMed  Google Scholar 

  13. Putzu GA, Figarella-Branger D, Bouvier-Labit CL, Bianco N, Pellissier JF (2000) Immunohistochemical localization of cytokines, C5b-9 and ICAM-1 in peripheral nerve of Guillain-Barré syndrome. J Neurol Sci 174:16–21

    Article  CAS  PubMed  Google Scholar 

  14. Rentzos M, Nikolaou C, Rombos A, Voumvourakis K, Segditsa I, Papageorgiou C (1996) Tumour necrosis factor alpha is elevated in serum and cerebrospinal fluid in multiple sclerosis and inflammatory neuropathies. J Neurol 243:165–170

    CAS  PubMed  Google Scholar 

  15. Schäfers M, Sommer C (2001) Diseases of the peripheral nervous system causing pain: Polyneuropathies. In: Sommer C (ed) Pain in peripheral nerve disease, Karger, Basel

  16. Schmidt B, Toyka KV, Kiefer R, Full J, Hartung HP, Pollard J (1996) Inflammatory infiltrates in sural nerve biopsies in Guillain-Barré syndrome and chronic inflammatory demyelinating neuropathy. Muscle Nerve 19:474–487

    Google Scholar 

  17. Sivieri S, Ferrarini AM, Lolli F, Mata S, Pinto F, Tavolato B, Gallo P (1997) Cytokine pattern in the cerebrospinal fluid from patients with GBS and CIDP. J Neurol Sci 147:93–95

    Article  CAS  PubMed  Google Scholar 

  18. Sommer C (2001) Cytokines and neuropathic pain. In: Hansson P, Fields H, Hill R, Marchettini P (eds) Neuropathic pain: pathophysiology and treatment, vol 21. IASP press, Seattle, pp 37–62

    Google Scholar 

  19. Stoll G, Jung S, Jander S, Meide P van der, Hartung H-P (1993) Tumor necrosis factor-alpha in immune-mediated demyelination and Wallerian degeneration of the rat peripheral nervous system. J Neuroimmunol 45:175–182

    CAS  PubMed  Google Scholar 

  20. Sundy JS, Haynes BF (2000) Cytokines and adhesion molecules in the pathogenesis of vasculitis. Curr Rheumatol Rep 2:402–410

    CAS  PubMed  Google Scholar 

  21. Yamamoto M, Ito Y, Mitsuma N, Li M, Hattori N, Sobue G (2001) Pathology-related differential expression regulation of NGF, GDNF, CNTF, and IL-6 mRNAs in human vasculitic neuropathy. Muscle Nerve 24:830–843

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

Supported by research funds of the University of Würzburg and by the Deutsche Forschungsgemeinschaft, SFB 353-B14. Barbara Dekant, Hiltrud Klüpfel and Sonja Peetz provided expert technical help. We thank K. Toyka for critical reading of the manuscript.

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Correspondence to Claudia Sommer.

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Lindenlaub, T., Sommer, C. Cytokines in sural nerve biopsies from inflammatory and non-inflammatory neuropathies. Acta Neuropathol 105, 593–602 (2003). https://doi.org/10.1007/s00401-003-0689-y

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  • DOI: https://doi.org/10.1007/s00401-003-0689-y

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