gms | German Medical Science

55. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie e. V. (DGNC)
1. Joint Meeting mit der Ungarischen Gesellschaft für Neurochirurgie

Deutsche Gesellschaft für Neurochirurgie (DGNC) e. V.

25. bis 28.04.2004, Köln

Immunosuppressive effects of steroids and non-steroidal anti-inflammatory drugs with anti-edema properties

Immunosuppression durch Steroide und nicht-steroidale Antiphlogistika mit antiödematöser Wirkung

Meeting Abstract

  • C. Ginzkey - Klinik für Neurochirurgie, Universitätsklinikum Schleswig-Holstein, Campus Kiel, Kiel
  • S. O. Eicker - Klinik für Neurochirurgie, Universitätsklinikum Schleswig-Holstein, Campus Kiel, Kiel
  • A. Heiser - Institut für Immunologie, Universitätsklinikum Schleswig-Holstein, Campus Kiel, Kiel
  • J. Steinmann - Institut für Immunologie, Universitätsklinikum Schleswig-Holstein, Campus Kiel, Kiel
  • H. M. Mehdorn - Klinik für Neurochirurgie, Universitätsklinikum Schleswig-Holstein, Campus Kiel, Kiel
  • corresponding author Wolfgang Hamel - Klinik für Neurochirurgie, Universitätsklinikum Schleswig-Holstein, Campus Kiel, Kiel

Deutsche Gesellschaft für Neurochirurgie. Ungarische Gesellschaft für Neurochirurgie. 55. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie e.V. (DGNC), 1. Joint Meeting mit der Ungarischen Gesellschaft für Neurochirurgie. Köln, 25.-28.04.2004. Düsseldorf, Köln: German Medical Science; 2004. DocDI.04.08

Die elektronische Version dieses Artikels ist vollständig und ist verfügbar unter: http://www.egms.de/de/meetings/dgnc2004/04dgnc0186.shtml

Veröffentlicht: 23. April 2004

© 2004 Ginzkey et al.
Dieser Artikel ist ein Open Access-Artikel und steht unter den Creative Commons Lizenzbedingungen (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.de). Er darf vervielf&aauml;ltigt, verbreitet und &oauml;ffentlich zug&aauml;nglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.


Gliederung

Text

Objective

Immuntherapy represents one approach to tackle infiltrating tumors such as gliomas. A great concern has been edema therapy with steroids which are potent inhibitors of T cell cytotoxicity. We assessed the immunosuppressive effect of steroids (dexamethasone) as well as alternative anti-inflammatory drugs with known anti-edema properties, including cyclooxygenase (COX)-1 (acetylsalicylic acid (ASA) and ibuprofen) and COX-2 prevalent inhibitors (parecoxib) as well as boswellic acids, a 5-lipoxygenase (5-LOX) inhibitor. To assess immunosuppression synthesis of IFN-γ, an important cytokine in T-cell dependent immunoreactivity, was quantified.

Methods

Lymphocytes were isolated from spleens of untreated Balb/c mice and stimulated with ConA (3 µg/ml) in 96-well PVDF-plates for 20 hours. Anti-inflammatory drugs to be tested were added at the same time in doses covering levels which are achieved in serum: dexamethasone 10-1000 ng/ml, acetylsalicylic acid 5-20 mM, ibuprofen 0.05-10 mM, and parecoxib 0.01-10 mM. Boswellic acids isolated in a 70% ethanol fraction from H15 (400 mg tablet/ml) were added to the culture medium in different concentrations (0.01-10.0%). IFN-γ synthesis was quantified by a commercially available ELISPOT assay (Diaclone, France).

Results

Dexamethasone in concentrations of 10, 100, and 1000 ng/ml decreased INF-γ production to 79.9, 43.4, and 18.8%, respectively. IFN-γ synthesis was also suppressed by ASA and ibuprofen: whereas ibuprofen showed complete suppression between 0.5 and 1.0 mM, ASA at 20 mM reduced IFN-γ to only 46.0%. Parecoxib when added at a concentration of 1.0 mM decreased IFN-γ synthesis to 63.2%, and complete suppression was acheived at 5.0 mM. Boswellic acids added at a concentration of ≥0.5% to the culture medium resulted in complete suppression of IFN-γ production. Taking serum levels commonly achieved in patients and the pharmacological properties of these drugs into account their immunosuppressive potency (excluding boswellia acids) in decreasing order is: dexamethasone >> ibuprofen > acetylsalicylic acid > parecoxib.

Conclusions

As expected, dexamethasone showed strong immunosuppressive effects. Nevertheless, immunosuppression was also observed with non-steroidal drugs, including COX-inhibitors as well as the 5-LOX-inhibitor boswellic acids. With respect to future immunotherapeutic trials acetylsalicylic acid and parecoxib which exerted the least immunosuppressive effects should be evaluated further in vivo.