Skip to main content
SpringerLink
Log in

Interleukin-2, soluble interleukin-2-receptor, neopterin,l-tryptophan and β2-microglobulin levels in CSF and serum of patients with relapsing-remitting or chronic-progressive multiple sclerosis

  • Original Communication
  • Published:
Journal of Neurology Aims and scope Submit manuscript

Abstract

Cerebrospinal fluid (CSF) and serum levels of interleukin-2 (IL-2), soluble IL-2 receptors (sIL-2R), neopterin,l-tryptophan (l-TRP) and β2-microglobulin ((β2-M) were measured in 31 untreated multiple sclerosis patients in acute exacerbation and 27 normal controls. Twenty-six patients showed the relapsing-remitting type of disease (RRMS); 5 had a chronic-progressive course (CPMS). No changes in serum IL-2 and sIL-2R were found between RRMS patients and controls, whereas serum and CSF levels as well as the CSF/serum ratio of neopterin were significantly elevated in the RRMS group. IL-2 was not detectable in CSF of patients or controls and sIL-2R levels were at the level of the lower detection (LD) sensitivity of the ELISA method. Four of 23 RRMS patients versus 1 of 25 controls showed CSF sIL-2R levels above the LD sensitivity, indicating a trend towards elevation in acute relapse. No difference was found in serum and CSFl-TRP and β2-M of patients and controls. In CSF of RRMS patients neopterin andl-TRP correlated negatively, reflecting the interferon-gamma mediated activation of macrophages in acute relapse. A significant positive correlation (Spearman rank 0.57,P = 0.001) between serum IL-2 levels and duration of acute relapse (mean 30 days) warrants further evaluation.

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. Adachi K (1989) Interleukin-2 receptor levels indicating relapse in multiple sclerosis. Lancet I:559–560

    Google Scholar 

  2. Adachi K, Kumamoto T, Araki S (1990) Elevated soluble interleukin-2 receptor levels with active multiple sclerosis. Ann Neurol 28:687–691

    PubMed  Google Scholar 

  3. Adachi N (1991) Beta-2-microglobulin levels in the cerebrospinal fluid: their value as a disease marker. Eur Neurol 31:181–185

    PubMed  Google Scholar 

  4. Bansil S, Troiano R, Cook SD, Rohowskykochan C (1991) Serum soluble interleukin-2 receptor levels in chronic progressive stable and steroid-treated multiple sclerosis. Acta Neurol Scand 84:282–285

    PubMed  Google Scholar 

  5. Barak M, Gruener N (1991) Neopterin augmentation of tumour necrosis factor production. Immunol Lett 30:101–106

    PubMed  Google Scholar 

  6. Bjerrum OW, Bach FW, Zeeberg I (1988) Increased level of cerebrospinal β2-microglobulin is related to neurologic impairment in multiple sclerosis. Acta Neurol Scand 78:72–75

    PubMed  Google Scholar 

  7. Brown RR, Borden EC, Sondel PM, Lee CM (1987) Effects of interferons and interleukin-2 on tryptophan metabolism in humans. In: Bender DA, Joseph MH, Kochen W, Steinhart H (eds) Progress in tryptophan and serotonin research 1986. De Gruyter, Berlin, pp 19–26

    Google Scholar 

  8. Demisch L, Proescholdt M, Ott M, Engelhardt W, Baas H, Fischer PA (1992) CSF tryptophan in inflammatory neurological diseases in relation to markers of cell-mediated immunity. Eur J Clin Chem Clin Biochem 30:A8

    Google Scholar 

  9. Dore-Duffy P, Ho SY, Donovan C (1991) Cerebrospinal fluid eicosanoid levels: endogenous PGD2 and LTC4 synthesis by antigen-presenting cells that migrate to the central nervous system. Neurology 41:322–324

    PubMed  Google Scholar 

  10. Fesenmeier JT, Whitaker JN, Herman PK, Walker DP (1991) Cerebrospinal fluid levels of myelin basic protein-like material and soluble interleukin-2 receptor in multiple sclerosis. J Neuroimmunol 34:77–80

    PubMed  Google Scholar 

  11. Fierz W, Dommasch D, Niederwieser A (1987) Neopterin in cerebro-spinal fluid as a parameter of local cellular immune reactions in the central nervous system. In: Lowenthal A (ed) Cellular and humoral immunological components of cerebrospinal fluid in MS. Plenum Press, New York, pp 369–379

    Google Scholar 

  12. Fredrikson S, Eneroth P, Link H (1987) Intrathecal production of neopterin in aseptic mengio-encephalitis and multiple sclerosis. Clin Exp Immunol 67:76–81

    PubMed  Google Scholar 

  13. Fredrikson S, Link H, Eneroth P (1987) CSF neopterin as a marker of disease activity in multiple sclerosis. Acta Neurol Scand 75:352–355

    PubMed  Google Scholar 

  14. Fuchs D, Moller AA, Reibnegger G, Werner ER, Werner-Felmayer G (1991) Increased endogenous interferon-gamma and neopterin correlate with increased degradation of tryptophan in human immunodeficiency virus type-1 infection. Immunol Lett 28:207–212

    PubMed  Google Scholar 

  15. Gallo P, Piccino M, Pagni S, Tavolato B (1988) Interleukin-2 levels in serum and cerebrospinal fluid of multiple sclerosis patients. Ann Neurol 24:795–797

    PubMed  Google Scholar 

  16. Gallo P, Piccinno MG, Pagni S, Argentiero V, Giometto B (1989) Immune activation in multiple sclerosis: study of IL-2, sIL-2R, and gamma-IFN levels in serum and cerebrospinal fluid. J Neurol Sci 92:9–15

    PubMed  Google Scholar 

  17. Gallo P, Piccinno MG, Tavolato B, Siden A (1991) A longitudinal study on IL-2, IL-2R, IL-4 and IFN-gamma in multiple sclerosis CSF and serum. J Neurol Sci 101:227–232

    PubMed  Google Scholar 

  18. Greenberg SJ, Marcon L, Hurwitz BJ, Waldmann TA (1988) Elevated levels of soluble interleukin-2 receptors in multiple sclerosis. N Engl J Med 319:1019–1020

    Google Scholar 

  19. Hartung HP, Hughes RAC, Taylor WA, Heininger K, Reiners K (1990) T cell activation in Guillain-Barré syndrome and in MS: elevated serum levels of soluble IL-2 receptors. Neurology 40:215–218

    PubMed  Google Scholar 

  20. Hayaishi O, Yoshida R, Takikawa O (1984) Indolamine dioxygenase: a possible biological function. In: Schlossberger HG, Kochen W, Linzen B, Steinhart H (eds) Progress in tryptophan and serotonin research. De Gruyter, Berlin, pp 33–42

    Google Scholar 

  21. Hofman FM, Hanwehr RI von, Dinarello CA, Mizel SB, Hinton D (1986) Immunoregulatory molecules and IL-2 receptors identified in multiple sclerosis brain. J Immunol 136:3239–3245

    PubMed  Google Scholar 

  22. Karlsson FA, Wibell L, Evrin PE (1980) β2-microglobulin in clinical medicine. Scand J Clin Lab Invest 40 [Suppl 154]:27–37

    PubMed  Google Scholar 

  23. Kurtzke JF (1983) Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology 33:1444–1452

    PubMed  Google Scholar 

  24. Lambin P, Lefrere J, Doinel C, Fine JM, Salmon D (1988) Neopterin and β2-microglobulin in serum of HIV-seropositive subjects during a two-year follow-up. Clin Chem 34:1367–1368

    PubMed  Google Scholar 

  25. Merrill J, Mohlstrom C, et al. (1984) Response to and production of interleukin 2 by peripheral blood and cerebrospinal fluid lymphocytes of patients with multiple sclerosis. J Immunol 133:1931–1937

    PubMed  Google Scholar 

  26. Peter JB, Boctor FN, Tourtellotte WW (1991) Serum and CSF levels of ILS-2, sIL-2R, TNF-alpha and IL1beta in chronic progressive multiple sclerosis: expected lack of clinical utility. Neurology 41:121–123

    PubMed  Google Scholar 

  27. Poser CM, Paty DW, Scheinberg L, McDonald I, Davis FA (1983) New diagnostic criteria for multiple sclerosis: guidelines for research protocols. Ann Neurol 13:227–231

    PubMed  Google Scholar 

  28. Proescholdt M, Demisch L, Enzensberger W, Fischer PA (1991) CSF beta2-microglobulin, neopterin and tryptophan levels in relation to neuromanifestations in HIV-infected subjects. J Neuroimmunol [Suppl] 1:199

    Google Scholar 

  29. Rudick RA, Ransohoff RM (1992) Cytokine secretion by multiple sclerosis monocytes. Relationship to disease activity. Arch Neurol 49:265–270

    PubMed  Google Scholar 

  30. Selmaj KW, Raine CS (1988) Tumor necrosis factor mediates myelin and obligodendrocyte damage in vitro. Ann Neurol 23:339–346

    PubMed  Google Scholar 

  31. Sharief MK, Thompson EJ (1992) In vivo relationship of tumour necrosis factor-alpha to blood-brain barrier damage in patients with active multiple sclerosis. J Neuroimmunol 38:27–33

    PubMed  Google Scholar 

  32. Shoedon G, Troppmair F, Adolf G, Huber C, Niederwieser A (1986) Interferon-gamma enhances biosynthesis of pterins in peripheral blood mononuclear cells by induction of GTP-cyclohydrolase I activity. J Interferon Res 6:697–703

    PubMed  Google Scholar 

  33. Traugott U (1987) Multiple sclerosis: relevance of Class I and Class II MHC-expressing cells to lesion development. J Neuroimmunol 16:283–302

    PubMed  Google Scholar 

  34. Trotter J, Clifford D, Anderson C et al (1988) Elevated serum interleukin-2 levels in chronic progressive multiple sclerosis. N Engl J Med 318:1206

    Google Scholar 

  35. Trotter JL, Clifford DB, McInnis JE (1989) Correlation of immunological studies and disease progression in chronic progressive multiple sclerosis. Ann Neurol 25:172–178

    PubMed  Google Scholar 

  36. Trotter JL, Collins KG, Vanderveen RC (1991) Serum cytokine levels in chronic progressive multiple sclerosis: interleukin-2 levels parallel tumor necrosis factor-alpha levels. J Neuroimmunol 33:29–36

    PubMed  Google Scholar 

  37. Viell B, Vestweber, Krause B (1988) Analysis of 5-OH-indoles in human gut biopsy tissues by reversed-phase high performance liquid chromatography with fluorimetric detection. J Pharm Biomed Anal 6:939–944

    Google Scholar 

  38. Wachter H, Fuchs D, Hausen A, Reibenegger G, Werner ER (1989) Neopterin as a marker for activation of cellular immunity: immunologic basis and clinical application. Adv Clin Chem 27:81–141

    PubMed  Google Scholar 

  39. Werner-Felmayer G, Werner ER, Fuchs D, Hausen A, Reibnegger G (1990) Neopterin formation and tryptophan degradation by a human myelomonocytic cell line (THP-1) upon cytokine treatment. Cancer Res 50:2863–2867

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Abteilung für Neurologie, Klinikum der Johann-Wolfgang-Goethe-Universität, Schleusenweg 2-16, D-60528, Frankfurt, Germany

    Melanie Ott, Lothar Demisch, Wolfram Engelhardt & Peter-Alexander Fischer

Authors
  1. Melanie Ott
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Lothar Demisch
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Wolfram Engelhardt
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Peter-Alexander Fischer
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ott, M., Demisch, L., Engelhardt, W. et al. Interleukin-2, soluble interleukin-2-receptor, neopterin,l-tryptophan and β2-microglobulin levels in CSF and serum of patients with relapsing-remitting or chronic-progressive multiple sclerosis. J Neurol 241, 108–114 (1993). https://doi.org/10.1007/BF00869773

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00869773

Key words

Search

Navigation