CSF interleukin 6 is a useful marker to distinguish pseudotumoral CNS inflammatory diseases from primary CNS lymphoma.
Cerebrospinal fluid
Inflammation
Interleukin 10
Interleukin 6
Primary central nervous system lymphoma
Journal
Journal of neurology
ISSN: 1432-1459
Titre abrégé: J Neurol
Pays: Germany
ID NLM: 0423161
Informations de publication
Date de publication:
Aug 2021
Aug 2021
Historique:
received:
29
11
2020
accepted:
08
02
2021
revised:
07
02
2021
pubmed:
21
2
2021
medline:
22
7
2021
entrez:
20
2
2021
Statut:
ppublish
Résumé
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). 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). 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. 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). 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.
Sections du résumé
BACKGROUND
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
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
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
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
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.
Identifiants
pubmed: 33609156
doi: 10.1007/s00415-021-10453-5
pii: 10.1007/s00415-021-10453-5
doi:
Substances chimiques
Biomarkers, Tumor
0
Interleukin-6
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
2890-2894Informations de copyright
© 2021. Springer-Verlag GmbH, DE part of Springer Nature.
Références
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
doi: 10.1101/cshperspect.a016295
pubmed: 25190079
pmcid: 4176007
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
doi: 10.1038/nature04753
pubmed: 16648838
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
doi: 10.1146/annurev.immunol.021908.132710
pubmed: 19132915
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
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
doi: 10.1007/s11060-014-1622-z
pubmed: 25258254
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
doi: 10.1172/JCI116977
pubmed: 8282815
pmcid: 293803
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
doi: 10.1093/neuonc/nor203
pubmed: 22156547
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
doi: 10.1016/j.ejca.2016.03.080
pubmed: 27156226
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
doi: 10.1182/blood-2013-01-476333
pubmed: 23570798
pmcid: 3674672
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
doi: 10.1111/bjh.15410
pubmed: 29808930
pmcid: 6099264
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
doi: 10.1080/17474086.2016.1242405
pubmed: 27677656
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
doi: 10.1177/1352458517717804
pubmed: 28657431
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
doi: 10.1111/bpa.12496
pubmed: 28213912
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
doi: 10.1212/WNL.0000000000008900
pubmed: 31907289
pmcid: 7238921
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
doi: 10.1016/S1470-2045(15)00076-5
pubmed: 26149884
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
doi: 10.1002/ajh.25578
pubmed: 31328307
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
doi: 10.1001/archneur.62.6.865
pubmed: 15956157
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
doi: 10.1371/journal.pone.0072399
pubmed: 24015240
pmcid: 3754988
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
doi: 10.1212/wnl.40.11.1735
pubmed: 2234430
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
doi: 10.1111/ene.13975
pubmed: 31021023
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
doi: 10.1016/0304-3940(94)90933-4
pubmed: 7845624
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
doi: 10.2174/1381612053381684
pubmed: 15777248