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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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
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
Dyck PJ, Benstead TJ, Conn DL, Stevens JC, Windebank AJ, Low PA (1987) Nonsystemic vasculitic neuropathy. Brain 110:843–854
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
Sundy JS, Haynes BF (2000) Cytokines and adhesion molecules in the pathogenesis of vasculitis. Curr Rheumatol Rep 2:402–410
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
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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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