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Cytokine expression in serum and cerebrospinal fluid in non-inflammatory polyneuropathies
  1. J Ludwig1,
  2. A Binder1,
  3. J Steinmann2,
  4. G Wasner1,
  5. R Baron1
  1. 1
    Division of Neurological Pain Research and Therapy, Department of Neurology, Universitätsklinikum Schleswig-Holstein, Campus Kiel, Kiel, Germany
  2. 2
    Department of Immunology, Universitätsklinikum Schleswig-Holstein, Campus Kiel, Kiel, Germany
  1. Dr Janne Ludwig, Division of Neurological Pain Research and Therapy, Department of Neurology, Universitätsklinikum Schleswig-Holstein, Campus Kiel, Schittenhelmstrasse 10, 24105 Kiel, Germany; j.ludwig{at}


Background: Pain is a common symptom in polyneuropathies (PNPs), although it is still not known why some PNPs are painful and others are painless. Increased pro-inflammatory cytokines have been found in conditions resulting in exaggerated pain states in animal studies. Recently, elevated pro-inflammatory cytokine levels have also been found in the cerebrospinal fluid (CSF) of patients suffering from complex regional pain syndrome. Pro-inflammatory cytokines have been shown to induce or increase inflammatory or neuropathic pain.

Methods: Using chemiluminescent enzyme immunometric assays, cytokine levels in 36 patients with painful and painless non-inflammatory PNPs in serum and CSF were investigated. The severity of PNPs was measured with electroneurography (ENG). In subjects with normal results using conventional ENG, quantitative thermo-testing was performed to investigate small-nerve-fibre function.

Results: Interleukin (IL)-6 and tumour necrosis factor (TNF)-α in serum or CSF did not differ between patients with (n = 18) or without (n = 18) painful PNPs, whereas patients with mechanical allodynia (n = 5) had elevated serum TNF-α levels compared to those without allodynia. TNF-α and IL-6 serum levels were higher in patients with severe (n = 21) compared to those with mild neuropathy (n = 15), and showed a positive correlation with severity of neuropathy.

Conclusions: Results suggest that nerve fibre degeneration and presence of mechanical allodynia in peripheral non-inflammatory neuropathy determine cytokine expression in serum.

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  • Competing interests: None declared.

  • Funding: Supported by the Bundesministerium für Bildung und Forschung (BMBF, 01EM05/04), the Deutsche Forschungsgemeinschaft (DFG Ba1921/1–1/3) and Pfizer Deutschland (unrestricted educational grant). None of the sponsors were involved in design and conduct of the study, in collection, management, analysis, interpretation and preparation of the data, review or approval of the manuscript.