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Increased pro-inflammatory cytokine gene expression in peripheral blood mononuclear cells of patients with polyneuropathies

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Abstract

Background

Distinct cytokine expression patterns have been reported in biomaterial of patients with polyneuropathies (PNP). We investigated gene expression profiles of pro- and anti-inflammatory cytokines in peripheral blood mononuclear cells (PBMC) of patients with neuropathies of different etiologies.

Methods

We prospectively studied 97 patients with neuropathies and compared data between diagnostic subgroups and healthy controls. Gene expression of a panel of pro- and anti-inflammatory cytokines was analyzed (interleukin-1 [IL-1], IL-2, IL-6, IL-8, tumor necrosis factor alpha [TNF], IL-4, and IL-10) in PBMC samples. Furthermore, protein levels of IL-6, IL-8, and TNF were measured in supernatant of PBMC stimulated with lipopolysaccharide (LPS).

Results

PNP were associated with higher PBMC gene expression of IL-1 (p < 0.05), IL-2 (p < 0.05), IL-8 (p < 0.001), and TNF (p < 0.01) compared to healthy controls. Inflammatory neuropathies were associated with higher gene expression of IL-8 (p < 0.001) and TNF (p < 0.05) and lower gene expression of IL-10 (p < 0.05) compared to healthy controls. More pro-inflammatory cytokines were elevated in painful neuropathy (IL-1, IL-2 [p < 0.05], IL-8 [p < 0.001] and TNF [p < 0.05]) than in painless neuropathy (IL-8 [p < 0.01] and TNF [p < 0.01]) compared to healthy controls, while IL-10 expression was higher in treatment naïve patients with painless neuropathy compared to patients with painful neuropathy (p < 0.05). Disease duration positively correlated with IL-6 gene expression (p < 0.01). Supernatant protein levels of IL-6, IL-8, and TNF did not differ between groups.

Conclusion

Systemic gene expression of pro-inflammatory cytokines is increased in patients with neuropathies and may be influenced by the presence of neuropathic pain.

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Acknowledgements

Expert technical help by S. Mildner is gratefully acknowledged. The study was supported by intramural funds of the University of Würzburg. This work is part of the doctoral thesis of M. Langjahr.

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Authors and Affiliations

  1. Department of Neurology, University of Würzburg, Josef-Schneider-Str. 11, 97080, Würzburg, Germany

    Melissa Langjahr, Anna-Lena Schubert, Claudia Sommer & Nurcan Üçeyler

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  1. Melissa Langjahr
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  2. Anna-Lena Schubert
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  4. Nurcan Üçeyler
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Correspondence to Nurcan Üçeyler.

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All human studies must state that they have been approved by the appropriate ethics committee and have therefore been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki.

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Langjahr, M., Schubert, AL., Sommer, C. et al. Increased pro-inflammatory cytokine gene expression in peripheral blood mononuclear cells of patients with polyneuropathies. J Neurol 265, 618–627 (2018). https://doi.org/10.1007/s00415-018-8748-4

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  • DOI: https://doi.org/10.1007/s00415-018-8748-4

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