Summary
This study was designed to investigate serum soluble interleukin-2 receptor (S-IL-2R), interleukin-2 (IL-2) and interleukin-6 levels (IL-6) in patients with either a positive or negativeBorrelia burgdorferi serology. Serum samples from 101 individuals, divided in to five groups according to clinical symptoms and outcome of serology were analysed. Samples of cerebrospinal fluid (CSF) from nine of the individuals were also studied. The highest average serum S-IL-2R levels (1,180+/−1,140 U/ml) were found in patients with erythema migrans, the hallmark of Lyme borreliosis, followed by patients with symptoms closely related toBorrelia infection (900+/−1,200 U/ml) and with a strong positive serology. In two patients with central nervous system (CNS) involvement, increased levels of S-IL-2R of 920 and 620 U/ml respectively (normal value <50 U/ml) were detected in the CSF. No statistically significant relationship between IgG or IgM antibody activity and serum S-IL-2R levels was found. Detectable levels of IL-2 were only found in three patients. Increased levels of IL-6 were found in sera from 14 patients. The highest concentration, 90 pg/ml (normal value <10 pg/ml), was measured in a patient presenting with vasculitis. In conclusion,B. burgdorferi infection causes a moderate increase of serum S-IL-2R levels, although there is no relationship between the severity of the infection, as estimated by the antibody concentration or to serum IL-2 or IL-6 levels. Secondary complications of the infection, such as vasculitis, may cause an increased level of serum IL-6. An increase of S-IL-2R levels may be found in the CSF during central nervous system involvement ofB. burgdorferi infection.
Zusammenfassung
Bei Patienten mit positiver oder negativerBorrelia burgdorferi-Serologie wurden die Serumspiegel von löslichem Interleukin-2 Rezeptor (S-IL-2R), Interleukin-2 (IL-2) und Interleukin-6 (IL-6) bestimmt. Die Serumproben von 101 Patienten wurden nach klinischen Symptomen und serologischen Testergebnissen in fünf Gruppen unterteilt und auf Zytokinspiegel untersucht. Von neun Patienten wurden auch Liquorproben untersucht. Die höchsten S-IL-2R-Spiegel (1 180±1 140 E/ml) fanden sich bei Erythema migrans, dem Leitsymptom der Lyme Borreliose. Es folgten Patienten, deren Symptome in engem Zusammenhang mit einer Borrelieninfektion standen mit Werten von 900±1 200 E/ml. Bei diesen Patienten lag auch eine deutliche Seroreaktion vor. Bei zwei Patienten mit ZNS-Beteiligung fanden sich erhöhte Spiegel an S-IL-2R im Liquor (920 beziehungsweise 620 E/ml; normale Spiegel < 50 E/ml). Zwischen IgG- oder IgM-Antikörperreaktivität und S-IL-2R- Serumspiegeln fand sich keine statistisch signifikante Beziehung. IL-2 konnte nur bei drei Patienten im Serum nachgewiesen werden. Bei 14 Patienten fanden sich erhöhte Spiegel von IL-6. Die höchste Serumkonzentration von IL-6 wurde bei einem Patienten mit Vaskulitis gemessen (90 pg/ml; Normalwert < 10 pg/ml). Aus den Daten läßt sich schließen, daß die Infektion mitB. burgdorferi mit einer mäßiggradigen Erhöhung der S-IL-2R-Spiegel im Serum einhergeht. Dabei besteht aber keine Beziehung zum Schweregrad der Infektion, gemessen an der Antikörperkonzentration oder IL-2- und IL-6-Serumspiegeln. Sekundäre Komplikationen der Infektion wie die Vaskulitis können mit einer Erhöhung des IL-6-Serumspiegels einhergehen. Während einerB. burgdorferi Infektion mit ZNS-Beteiligung kann im Liquor ein Anstieg des S-IL-2R-Spiegels nach-gewiesen werden.
Similar content being viewed by others
References
Steere, A. C., Grodzicki, R. L., Kornblatt, J. E., Barbour, A. B., Burgdorfer, W., Schmid, G. P., Johnson, E., Malawista, S. The spirochetal etiology of Lyme disease. N. Engl. J. Med. 308 (1983) 733–740.
Burgdorfer, W., Barbour, A. G., Hayes, S. F., Benach, J. L., Grunwaldt, E., Davis, J. P. Lyme disease — a tickborne spirochetosis? Science 216 (1982) 1317–1319.
Steere, A. C. Lyme disease. N. Engl. J. Med. 321 (1989) 586–596.
Steere, A. C., Malawista, S. E., Hardin, J. A., Ruddy, S., Askenase, W., Andiman, W. A. Erythema cronicum migrans and Lyme arthritis: the enlarging clinical spectrum. Ann. Intern. Med. 86 (1977) 685–698.
Pachner, A. R., Steere, A. C. The triad of neurologic manifestations of Lyme disease: meningitis, cranial neuritis and radiculoneuritis. Neurology 35 (1985) 47–53.
Malawista, S. E., Steere, A. C. Lyme disease: infectious in origin, rheumatic in expression. Adv. Interm. Med. 31 (1986) 147–166.
Russell, H., Sampson, J. S., Schmid, G. P., Wilkinson, H. W., Plikaytis, B. Enzyme-linked immunosorbent assay and indirect immunofluorescence assay for Lyme disease. J. Infect. Dis. 149 (1984) 465–470.
Rose, C., Fawcett, P., Dubbs, S., Doughty, R. Use of Western blot and enzyme-linked immunosorbent assays to assist in the diagnosis of Lyme disease. Pediatrics 88 (1991) 465–470.
Brucebauer, H. R., Preac-Mursic, V., Fuchs, R., Wilske, B. Cross-reactive proteins ofBorrelia burgdorferi. Eur. J. Infect. Dis. 3 (1992) 224–232.
Miller, L. C., Isa, S., Vannier, E., Georgilis, K., Steere, A. C., Dinarello, C. A. LiveBorrelia burgdorferi: preferentially activate IL-1b gene expression and protein synthesis over the interleukin-1 receptor antagonist. J. Clin. Invest. 90 (1992) 906–912.
Miller, L. C., Lynch, E. A., Isa, S., Logan, I. W., Dinarello, C. A., Steere, A. C. Balance of synovial fluid IL-1b and IL-1 receptor antagonist and recovery from Lyme arthritis. Lancet 341 (1993) 146–148.
Åsbrink, E., Hovmark, A. The spirochetal etiology of acrodermatitis chronica atrophicans Herxheimer. Acta Derm. Venereol. 64 (1984) 506–512.
Grodzicki, R. L., Steere A. C. Comparison of immunoblotting and indirect enzyme-linked immunosorbent assay using different preparations for diagnosing early Lime disease. J. Infect Dis. 157 (1988) 790–797.
Nässberger, L. Serum levels of interleukin-6 are not dependent on the kidney function. Med. Inflam. 1 (1992) 197–200.
Nässberger, L., Träskman Bendz, L. Increased soluble interleukin-2 receptor concentrations in suicide attempters. Acta Psychiatr. Scand. 88 (1993) 48–52.
Mannoussakis, M. N., Papadopoulos, G. K., Drosos, A. A., Moulsopoulos, H. M. Soluble interleukin 2 receptor molecules in the serum of patients with autoimmune diseases. Clin. Immunol. Immunopathol. 50 (1989) 321–332.
Lawrance, E. C., Holland, V. A., Young, J. B., Windsor, N. T., Brousseau, K. P., Noon, G. P., Whiesennaud, H. H., Debakey, M. E., Nelson, K. L. Dynamic changes in soluble interleukin-2 receptor levels after lung or heart-lung transplantation. Am. Rev. Respir. Dis. 140 (1989) 789–796.
Chilosi, M., Semenzato, G., Vinante, F. Increased levels of soluble interleukin-2 receptor in non-Hodgkin's lymphomas. Relationship with clinical histologic and phenotyphic features. Am. J. Clin. Pathol. 92 (1989) 186–191.
Honda, M., Kitamura, K., Matsuda, K., Yokota, Y., Yamamoto, I. V., Mitsuyasu, R., Cherman, J. C., Tokungai, T. Soluble IL-2 receptor in AIDS. Correlation of its serum level with the classification of HIV-induced diseases and its characterization. Infect. Immun. 142 (1989) 4248–4255.
Zoschke, D. C., Skemp, A. A., Defosse, D. C. Lympho proliferative responses toBorrelia burgdorferi in Lyme disease. Ann. Int. Med. 114 (1991) 285–289.
Fawcett, P. T., Rose, C. D., Proujansky, R., Gibney, K. M., Molloy, D. M., Doughty, R. A. Serial measurements of soluble interleukin 2 receptor levels: an early indicator of treatment response for Lyme disease. J. Rheumatol. 20 (1993) 996–998.
Nässherger, L., Sturfelt, G., Thysell, H. Serum levels of the soluble-interleukin-2 receptor are dependent on the kidney function. Am. J. Nephrol. 12 (1993) 401–405.
Garcia-Monco, J. C., Villar, B. F., Alen, J. C., Benach, J. L. Borrelia burgdorferi in the central nervous system: experimental and clinical evidence for early invasion. J. Infect. Dis. 161 (1990) 1187–1193.
Vacca, A., Distefaud, R., Frassanito, A., Jodice, G., Dammacco, F. A disturbance of the IL-2/IL-2 receptor system parallels the activity of multiple myeloma. Clin. Exp. Immunol. 84 (1991) 429–434.
Yssel, H., Shanafelt, M.-C., Soderberg, C., Schneider, P. V., Anzda, J., Petz, G. Borrelia burgdorferi activates a T helper type 1-like T-cell subset in Lyme arthritis. J. Exp. Med. 174 (1991) 593–601.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Nilsson, I., Alves, M. & Nässberger, L. Response of soluble IL-2 receptor, interleukin-2 and interleukin-6 in patients with positive and negativeBorrelia burgdorferi serology. Infection 22, 316–320 (1994). https://doi.org/10.1007/BF01715535
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01715535