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CSF interleukin 6 is a useful marker to distinguish pseudotumoral CNS inflammatory diseases from primary CNS lymphoma

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Abstract

Background

Interleukin 6 (IL-6) is a pleomorphic cytokine that can be found in the cerebrospinal fluid (CSF) in a wide spectrum of inflammatory pathologies of the central nervous system (CNS).

Objective

Our aim was to characterize the diagnostic significance of CSF IL-6 among various CNS inflammatory diseases with pseudotumoral lesions (CNSID) and primary CNS lymphoma (PCNSL).

Methods

We retrospectively analyzed the CSF IL-6 concentrations in 43 consecutive patients with suspected PCNSL. A total of 28 patients were positively diagnosed with PCNSL and 15 with CNSID. We verified the results with CSF IL-10, an established biomarker for PCNSL.

Results

In the PCNSL group, the median CSF IL-6 concentration was 8 pg/ml, interquartile range (IQR) 5–18.5. For the patients with CNSID, the median concentration was 70 pg/ml, IQR 5–1368. A group comparison showed significantly higher CSF IL-6 levels in patients with CNSID than in those with PCNSL (p = 0.032). Moreover, IL-6 was correlated with CSF cell count in the CNSID group (r = 0.56, p = 0.028), but not in the PCNSL group (r = 0.3, p = 0.13).

We found significantly higher CSF IL-10 levels in patients with PCNSL than in patients with CNS inflammatory lesions (p < 0.001).

Discussion and conclusions

Our study suggests that CSF IL-6 levels could represent, in addition to CSF IL-10, a useful biomarker in the differential diagnosis of CNSID and suspected PCNSL.

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References

  1. Tanaka T, Narazaki M, Kishimoto T (2014) IL-6 in inflammation, immunity, and disease. Cold Spring Harb Perspect Biol 6(10):a016295. https://doi.org/10.1101/cshperspect.a016295

    Article  PubMed  PubMed Central  Google Scholar 

  2. Bettelli E, Carrier Y, Gao W, Korn T, Strom TB, Oukka M, Weiner HL, Kuchroo VK (2006) Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells. Nature 441(7090):235–238. https://doi.org/10.1038/nature04753

    Article  CAS  PubMed  Google Scholar 

  3. Korn T, Bettelli E, Oukka M, Kuchroo VK (2009) IL-17 and Th17 Cells. Annu Rev Immunol 27:485–517. https://doi.org/10.1146/annurev.immunol.021908.132710

    Article  CAS  PubMed  Google Scholar 

  4. Okada M, Kitahara M, Kishimoto S, Matsuda T, Hirano T, Kishimoto T (1988) IL-6/BSF-2 functions as a killer helper factor in the in vitro induction of cytotoxic T cells. Journal of Immunology 141(5):1543–1549

    CAS  Google Scholar 

  5. Sasagawa Y, Akai T, Tachibana O, Iizuka H (2015) Diagnostic value of interleukin-10 in cerebrospinal fluid for diffuse large B-cell lymphoma of the central nervous system. J Neurooncol 121(1):177–183. https://doi.org/10.1007/s11060-014-1622-z

    Article  CAS  PubMed  Google Scholar 

  6. Levy Y, Brouet JC (1994) Interleukin-10 prevents spontaneous death of germinal center B cells by induction of the bcl-2 protein. J Clin Investig 93(1):424–428. https://doi.org/10.1172/JCI116977

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Sasayama T, Nakamizo S, Nishihara M, Kawamura A, Tanaka H, Mizukawa K, Miyake S, Taniguchi M, Hosoda K, Kohmura E (2012) Cerebrospinal fluid interleukin-10 is a potentially useful biomarker in immunocompetent primary central nervous system lymphoma (PCNSL). Neuro-oncology 14(3):368–380. https://doi.org/10.1093/neuonc/nor203

    Article  CAS  PubMed  Google Scholar 

  8. Nguyen-Them L, Costopoulos M, Tanguy ML, Houillier C, Choquet S, Benanni H, Elias-Shamieh R, Armand M, Faivre G, Glaisner S, Malak S, Vargaftig J, Hoang-Xuan K, Ahle G, Touitou V, Cassoux N, Davi F, Merle-Beral H, Le Garff-Tavernier M, Soussain C, French LOC Network for CNS Lymphoma (2016) The CSF IL-10 concentration is an effective diagnostic marker in immunocompetent primary CNS lymphoma and a potential prognostic biomarker in treatment-responsive patients. Eur J Cancer 61:69–76. https://doi.org/10.1016/j.ejca.2016.03.080

    Article  CAS  PubMed  Google Scholar 

  9. Rubenstein JL, Wong VS, Kadoch C, Gao HX, Barajas R, Chen L, Josephson SA, Scott B, Douglas V, Maiti M, Kaplan LD, Treseler PA, Cha S, Hwang JH, Cinque P, Cyster JG, Lowell C (2013) CXCL13 plus interleukin 10 is highly specific for the diagnosis of CNS lymphoma. Blood 121(23):4740–4748. https://doi.org/10.1182/blood-2013-01-476333

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. van Westrhenen A, Smidt LCA, Seute T, Nierkens S, Stork ACJ, Minnema MC, Snijders TJ (2018) Diagnostic markers for CNS lymphoma in blood and cerebrospinal fluid: a systematic review. Br J Haematol 182(3):384–403. https://doi.org/10.1111/bjh.15410

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Korfel A, Nowosielski M, Pardo-Moreno J, Penalver FJ, Buda G, Bennani H, Costopoulos M, Le Garff-Tavernier M, Soussain C, Schmid M, Orfao JA, Glantz M (2016) How to facilitate early diagnosis of CNS involvement in malignant lymphoma. Expert Rev Hematol 9(11):1081–1091. https://doi.org/10.1080/17474086.2016.1242405

    Article  CAS  PubMed  Google Scholar 

  12. Ikeguchi R, Shimizu Y, Shimizu S, Kitagawa K (2018) CSF and clinical data are useful in differentiating CNS inflammatory demyelinating disease from CNS lymphoma. Multiple Sclerosis 24(9):1212–1223. https://doi.org/10.1177/1352458517717804

    Article  PubMed  Google Scholar 

  13. Barrantes-Freer A, Engel AS, Rodriguez-Villagra OA, Winkler A, Bergmann M, Mawrin C, Kuempfel T, Pellkofer H, Metz I, Bleckmann A, Hernandez-Duran S, Schippling S, Rushing EJ, Frank S, Glatzel M, Matschke J, Hartmann C, Reifenberger G, Muller W, Schildhaus HU, Bruck W, Stadelmann C (2018) Diagnostic red flags: steroid-treated malignant CNS lymphoma mimicking autoimmune inflammatory demyelination. Brain Pathol 28(2):225–233. https://doi.org/10.1111/bpa.12496

    Article  CAS  PubMed  Google Scholar 

  14. Houillier C, Soussain C, Ghesquieres H, Soubeyran P, Chinot O, Taillandier L, Lamy T, Choquet S, Ahle G, Damaj G, Agape P, Molucon-Chabrot C, Amiel A, Delwail V, Fabbro M, Jardin F, Chauchet A, Moles-Moreau MP, Morschhauser F, Casasnovas O, Gressin R, Fornecker LM, Abraham J, Marolleau JP, Tempescul A, Campello C, Colin P, Tamburini J, Laribi K, Serrier C, Haioun C, Chebrek S, Schmitt A, Blonski M, Houot R, Boyle E, Bay JO, Oberic L, Tabouret E, Waultier A, Martin-Duverneuil N, Touitou V, Cassoux N, Kas A, Mokhtari K, Charlotte F, Alentorn A, Feuvret L, Le Garff-Tavernier M, Costopoulos M, Mathon B, Peyre M, Delgadillo D, Douzane H, Genet D, Aidaoui B, Hoang-Xuan K, Gyan E (2020) Management and outcome of primary CNS lymphoma in the modern era: an LOC network study. Neurology 94(10):e1027–e1039. https://doi.org/10.1212/WNL.0000000000008900

    Article  PubMed  PubMed Central  Google Scholar 

  15. Hoang-Xuan K, Bessell E, Bromberg J, Hottinger AF, Preusser M, Ruda R, Schlegel U, Siegal T, Soussain C, Abacioglu U, Cassoux N, Deckert M, Dirven CM, Ferreri AJ, Graus F, Henriksson R, Herrlinger U, Taphoorn M, Soffietti R, Weller M, European Association for Neuro-Oncology Task Force on Primary CNSL (2015) Diagnosis and treatment of primary CNS lymphoma in immunocompetent patients: guidelines from the European association for neuro-oncology. Lancet Oncol 16(7):e322-332. https://doi.org/10.1016/S1470-2045(15)00076-5

    Article  PubMed  Google Scholar 

  16. Armand M, Costopoulos M, Osman J, Tarfi S, Houillier C, Choquet S, Agnelo H, Bonnemye P, Ronez E, Settegrana C, Soussain C, Hoang-Xuan K, Le Garff-Tavernier M, Davi F (2019) Optimization of CSF biological investigations for CNS lymphoma diagnosis. Am J Hematol 94(10):1123–1131. https://doi.org/10.1002/ajh.25578

    Article  PubMed  Google Scholar 

  17. Freedman MS, Thompson EJ, Deisenhammer F, Giovannoni G, Grimsley G, Keir G, Ohman S, Racke MK, Sharief M, Sindic CJ, Sellebjerg F, Tourtellotte WW (2005) Recommended standard of cerebrospinal fluid analysis in the diagnosis of multiple sclerosis: a consensus statement. Arch Neurol 62(6):865–870. https://doi.org/10.1001/archneur.62.6.865

    Article  PubMed  Google Scholar 

  18. Wullschleger A, Kapina V, Molnarfi N, Courvoisier DS, Seebach JD, Santiago-Raber ML, Hochstrasser DF, Lalive PH (2013) Cerebrospinal fluid interleukin-6 in central nervous system inflammatory diseases. PLoS ONE 8(8):e72399. https://doi.org/10.1371/journal.pone.0072399

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Hauser SL, Doolittle TH, Lincoln R, Brown RH, Dinarello CA (1990) Cytokine accumulations in CSF of multiple sclerosis patients: frequent detection of interleukin-1 and tumor necrosis factor but not interleukin-6. Neurology 40(11):1735–1739. https://doi.org/10.1212/wnl.40.11.1735

    Article  CAS  PubMed  Google Scholar 

  20. Chazal T, Costopoulos M, Maillart E, Fleury C, Psimaras D, Legendre P, Pineton de Chambrun M, Haroche J, Lubetzki C, Amoura Z, Legarff-Tavernier M, Cohen Aubart F (2019) The cerebrospinal fluid CD4/CD8 ratio and interleukin-6 and -10 levels in neurosarcoidosis: a multicenter, pragmatic, comparative study. Eur J Neurol 26(10):1274–1280. https://doi.org/10.1111/ene.13975

    Article  CAS  PubMed  Google Scholar 

  21. Banks WA, Kastin AJ, Gutierrez EG (1994) Penetration of interleukin-6 across the murine blood-brain barrier. Neurosci Lett 179(1–2):53–56. https://doi.org/10.1016/0304-3940(94)90933-4

    Article  CAS  PubMed  Google Scholar 

  22. Banks WA (2005) Blood-brain barrier transport of cytokines: a mechanism for neuropathology. Curr Pharm Des 11(8):973–984. https://doi.org/10.2174/1381612053381684

    Article  CAS  PubMed  Google Scholar 

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Funding

This research was not supported by any funding.

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Authors and Affiliations

  1. Service de Neurologie, Hôpitaux Civils de Colmar, Colmar, France

    Aurelian Ungureanu, Timothée Parratte, Abdelmalek Brinet, Hélène Durand, Claude Gaultier, François Sellal & Guido Ahle

  2. Service d’Hématologie Biologique, Hôpital Pitié-Salpêtrière, AP-HP, Paris, France

    Magali Le Garff-Tavernier & Myrto Costopoulos

  3. Laboratoire d’Hématologie, Hôpitaux Civils de Colmar, Colmar, France

    Remy Hurstel & Isabelle Alamome

  4. Service de Neurologie, Hôpital Saint Antoine et Hôpital Pitié Salpêtrière, AP-HP, 184 Faubourg de Saint Antoine, 75012, Paris, France

    Aurelian Ungureanu

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  1. Aurelian Ungureanu
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  2. Magali Le Garff-Tavernier
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  11. Guido Ahle
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Contributions

Contributions to the conception or design of the work, acquisition, analysis and interpretation of data (AU, GA); performed cytokine assays (MLGT, MC); drafted the work or revised it critically for important intellectual content (MC, TP, AB, HD, CG, RH, IA, FS, MLGT).

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Correspondence to Aurelian Ungureanu.

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Ungureanu, A., Le Garff-Tavernier, M., Costopoulos, M. et al. CSF interleukin 6 is a useful marker to distinguish pseudotumoral CNS inflammatory diseases from primary CNS lymphoma. J Neurol 268, 2890–2894 (2021). https://doi.org/10.1007/s00415-021-10453-5

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  • DOI: https://doi.org/10.1007/s00415-021-10453-5

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