Skip to main content

Advertisement

SpringerLink
Log in

Intrathecal levels of IL-6, IL-11 and LIF in Alzheimer's disease and frontotemporal lobar degeneration

  • ORIGINAL COMMUNICATION
  • Published:
Journal of Neurology Aims and scope Submit manuscript

Abstract

Cerebrospinal fluid (CSF) levels of interleukin (IL)-6, IL-11 and leukaemia inhibitory factor (LIF) were evaluated in 43 patients with Alzheimer's disease (AD) and 24 patients with frontotemporal lobar degeneration (FTLD) as compared with 30 agematched controls (CON), and correlated with clinical and demographic data and with CSF biomarkers amyloid beta (Aβ)42, total tau and tau phosphorylated at position 181 (P-tau). CSF IL-11 mean levels were significantly increased in AD and FTLD as compared with CON (6.5 ± 4.6 and 6.6 ± 5.1 versus 3.1 ± 3.3 pg/ml, P = 0.009). IL-6 mean levels did not differ between patients and CON (P > 0.05),whereas LIF levels were not detectable in patients or in CON. In AD patients, a significantly positive correlation between MMSE scores and IL-11 CSF concentration was observed (r = 0.344, P = 0.028). No correlations with CSF Aβ42, total tau and P-tau were found. IL-11, but not IL-6 levels are increased in AD and FTLD, and the highest peaks were observed in patients with a less severe degree of cognitive deterioration, therefore suggesting a role of this cytokine in early phases of neurodegeneration.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Akiyama H, Barger S, Barnum S, Bradt B, Bauer J, Cole GM, et al. (2000) Inflammation and Alzheimer’s disease. Neurobiol Aging 21:383–421

    Article  PubMed  CAS  Google Scholar 

  2. Andreasen N, Blennow K (2005) CSF biomarkers for mild cognitive impairment and early Alzheimer’s disease. Clin Neurol Neurosurg 107:165–173

    Article  PubMed  Google Scholar 

  3. Araujo DM, Cotman CW (1993) Trophic effects of interleukin-4, –7 and –8 on hippocampal neuronal cultures: potential involvement of glial-derived factors. Brain Res 600:49–55

    Article  PubMed  CAS  Google Scholar 

  4. Blum-Degen D, Müller T, Kuhn W, Gerlach M, Przuntek H, Riederer P (1995) Interleukin-1 β and interleukin- 6 are elevated in the cerebrospinal fluid of Alzheimer’s and de novo Parkinson’s disease patients. Neurosci Lett 202:17–20

    Article  PubMed  CAS  Google Scholar 

  5. Fann MJ, Patterson PH (1994) Neuropoietic cytokines and activin A differentially regulate the phenotype of cultured symphatetic neurons. Proc Natl Acad Sci USA 91:43–47

    Article  PubMed  CAS  Google Scholar 

  6. Fenoglio C, Galimberti D, Lovati C, Guidi I, Gatti A, Fogliarino S, et al. (2004) MCP-1 in Alzheimer's disease patients: A-2518G polymorphism and serum levels. Neurobiol Aging 25:1169–1173

    Article  PubMed  CAS  Google Scholar 

  7. Galimberti D, Schoonenboom N, Scarpini E, Scheltens P, on behalf of the Dutch-Italian Alzheimer Research Group (2003) Chemokines in serum and cerebrospinal fluid of Alzheimer’s disease patients. Ann Neurol 53(4):547–548

    Article  PubMed  Google Scholar 

  8. Galimberti D, Schoonenboom N, Scheltens P, Fenoglio C, Venturelli E, Pijnenburg YAL, et al. (2006) Intrathecal chemokine levels in Alzheimer disease and frontotemporal lobar degeneration. Neurology 66:146–147

    Article  PubMed  CAS  Google Scholar 

  9. Galimberti D, Schoonenboom N, Scheltens P, Fenoglio C, Bouwman F, Venturelli E, et al. (2006) Intrathecal chemokine synthesis in mild cognitive impairment and Alzheimer disease. Arch Neurol 63(4):538–543

    Article  PubMed  Google Scholar 

  10. Heese K, Nagai Y, Tohru S (2000). Induction of rat L-phosphoserine phosphatase by amyloid-β (1–42) is inhibited by interleukin-11. Neurosci Lett 288:37–40

    Article  PubMed  CAS  Google Scholar 

  11. Iwatsubo T, Odaka A, Suzuki N, Mizusawa H, Nukina N, Ihara Y (1994) Visualization of A beta 42(43) and A beta 40 in senile plaques with endspecific A beta monoclonals: evidence that an initially deposited species is A beta 42(43). Neuron 13:45–53

    Article  PubMed  CAS  Google Scholar 

  12. Jia JP, Meng R, Sun YX, Sun WJ, Ji XM, Jia LF (2005) Cerebrospinal fluid tau, Ab 1–42 and inflammatory cytokines in patients with Alzheimer’s disease and vascular dementia. Neurosci Lett 383:12–16

    Article  PubMed  CAS  Google Scholar 

  13. Kalehua AN, Nagel JE, Whelchel LM, Gides JJ, Pyle RS, Smith RJ, et al. (2004) Monocyte chemoattractant protein-1 and macrophage inflammatory protein-2 are involved in both excitotoxininduced neurodegeneration and regeneration. Exp Cell Res 297:197–211

    Article  PubMed  CAS  Google Scholar 

  14. Leng SX, Elias JA (1997) Molecules in focus. Interleukin-11. Int J Biochem Cell. Biol 29:1059–1062

    Article  PubMed  CAS  Google Scholar 

  15. Markesbery WR, Schmitt FA, Kryscio RJ, Davis DG, Smith CD, Wekstein DR (2006) Neuropathologic substrate of mild cognitive impairment. Arch Neurol 63(1):38–46

    Article  PubMed  Google Scholar 

  16. März P, Heese K, Hock C, Golombowski S, Muller-Spahn F, Rose-John S, Otten U (1997) Interleukin-6 (IL-6) and soluble forms of IL-6 receptors are not altered in cerebrospinal fluid of Alzheimer’s disease patients. Neurosci Lett 239:29–32

    Article  PubMed  Google Scholar 

  17. McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM (1984) Clinical diagnosis of Alzheimer’s disease: Report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer’s Disease. Neurology 34:939–944

    PubMed  CAS  Google Scholar 

  18. Mehler MF, Rozental R, Dougherty M, Spray DC, Kesslerm JA (1993) Cytokine regulation of neuronal differentiation of hippocampal progenitor cells. Nature 362:62–65

    Article  PubMed  CAS  Google Scholar 

  19. Morris JC, Storandt M, Miller JP, McKeel DW, Price JL, Rubin EH, Berg L (2001) Mild cognitive impairment represents early-stage Alzheimer’s disease. Arch Neurol 58:397–405

    Article  PubMed  CAS  Google Scholar 

  20. Neary D, Snowden JS, Gustafson L, Passant U, Stuss D, Black S, et al. (1998) Frontotemporal lobar degeneration. A consensus on clinical diagnostic criteria. Neurology 51:1546–1554

    PubMed  CAS  Google Scholar 

  21. Petersen RC, Smith GE, Waring SC, Ivnik RJ, Tangalos EG, Kokmen E (1999) Mild cognitive impairment: clinical characterization and outcome. Arch Neurol 56:303–308

    Article  PubMed  CAS  Google Scholar 

  22. Richartz E, Stransky E, Batra A, Simon P, Lewczuk P, Buchkremer G, et al. (2005) Decline of immune responsiveness: a pathogenetic factor in Alzheimer’s disease? J Psychiatr Res 39(5):535–543

    Article  PubMed  Google Scholar 

  23. Sellebjerg F, Christiansen M (1996) Qualitative assessment of intrathecal IgG synthesis by isoelectric focusing and immunodetection: interlaboratory reproducibility and interobserver agreement. Scand J Clin Lab Invest 56:135–143

    Article  PubMed  CAS  Google Scholar 

  24. Simon R, Thier M, Kruttgen A, Rose- John S, Weiergraber O, Heinrich PC, et al. (1995) Human CNTF and related cytokines: effects on DRG neurone survival. Neuroreport 7:153–157

    PubMed  CAS  Google Scholar 

  25. Sjögren M, Folkesson S, Blennow K, Tarkowski E (2004) Increased intrathecal inflammatory activity in frontotemporal dementia: pathophysiological implications. J Neurol Neurosurg Psychiatry 75:1107–1111

    Article  PubMed  Google Scholar 

  26. Taga T, Kishimoto T (1997) Gp130 and the interleukin-6 family of cytokines. Annu Rev Immunol 15:797–819

    Article  PubMed  CAS  Google Scholar 

  27. Tarkowski E, Wallin A, Blennow K, Tarkowski A (1999) Intracerebral production of tumor necrosis factoralpha, a local neuroprotective agent, in Alzheimer disease and vascular dementia. J Clin Immunol 19:223–230

    Article  PubMed  CAS  Google Scholar 

  28. Tarkowski E, Liljeroth AM, Minthon L, Tarkowski A, Wallin A, Blennow K (2003) Cerebral pattern of pro- and anti-inflammatory cytokines in dementias. Brain Res Bull 61(3):255–260

    Article  PubMed  CAS  Google Scholar 

  29. The Italian Longitudinal Study on Aging (1997) Prevalence of chronic diseases in older Italians: comparing self-reported and clinical diagnosis. Internat J Epidemiol 26:995–1002

    Article  Google Scholar 

  30. Thier M, Hall M, Heath JK, Pennica D, Weis J (1999) Trophic effects of cardiotrophin- 1 and interleukin-11 on rat dorsal root ganglion neurons in vitro. Mol Brain Res 64:80–84

    Article  PubMed  CAS  Google Scholar 

  31. Wada-Isoe K, Wakutani Y, Urakami K, Nakashima K (2004) Elevated interleukin- 6 levels in cerebrospinal fluid of vascular dementia patients. Acta Neurol Scand 110:124–127

    Article  PubMed  CAS  Google Scholar 

  32. Xia MQ, Hyman BT (1999) Chemokines/chemokine receptors in the central nervous system and Alzheimer’s disease. J Neurovirol 5:32–41

    Article  PubMed  CAS  Google Scholar 

  33. Yamada K, Kono K, Umegaki H, Yamada K, Iguchi A, Fukatsu T, et al. (1995) Decreased interleukin-6 level in the cerebrospinal fluid of patients with Alzheimer-type dementia. Neurosci Lett 186:219–221

    Article  PubMed  CAS  Google Scholar 

  34. Yang, YC (1993) Interleukin 11: an overview. Stem Cells 11:474–486

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Dept. of Neurological Sciences, "Dino Ferrari" Center, University of Milan, IRCCS Ospedale Maggiore Policlinico, Via F. Sforza 35, 20122, Milan, Italy

    D. Galimberti, E. Venturelli, C. Fenoglio, I. Guidi, C. Villa, F. Cortini, D. Scalabrini, P. Baron, N. Bresolin & E. Scarpini

  2. Dept. of Internal Medicine, Geriatric Unit, University of Milan, IRCCS Ospedale Maggiore Policlinico, Via F. Sforza 35, 20122, Milan, Italy

    L. Bergamaschini & C. Vergani

Authors
  1. D. Galimberti
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. E. Venturelli
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. C. Fenoglio
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. I. Guidi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. C. Villa
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. L. Bergamaschini
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. F. Cortini
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. D. Scalabrini
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. P. Baron
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. C. Vergani
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. N. Bresolin
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. E. Scarpini
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to D. Galimberti.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Galimberti, D., Venturelli, E., Fenoglio, C. et al. Intrathecal levels of IL-6, IL-11 and LIF in Alzheimer's disease and frontotemporal lobar degeneration. J Neurol 255, 539–544 (2008). https://doi.org/10.1007/s00415-008-0737-6

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00415-008-0737-6

Key words

Search

Navigation