Aktuelle Neurologie 2009; 36 - P677
DOI: 10.1055/s-0029-1238770

Classical conditioning of the immune system using mitoxantrone

G Mina 1, E Tolosa 1, M Hagemann-Goebel 1, R Martin 1, C Heesen 1
  • 1Hamburg

Mitoxantrone (MX) is a cytostatic drug that is used in the treatment of multiple sclerosis (MS) as an escalation therapy when other immunomodulatory treatment options have failed. Treatment with MX can lead to a number of side effects, but especially the cardiotoxicity of MX requires careful monitoring and limits the treatment duration. Animal and human studies have demonstrated that after classical conditioning procedures using an immunmodulatory drug (e.g. cyclosporine A) as the unconditioned stimulus (UCS) paired with a novel, salient taste (e.g. saccharine) as the conditioned stimulus (CS), re-presentation of the CS alone leads to changes in the immune system similar to the drug effects (e.g. Ader and Cohen, Science 1982; Goebel et al., FASEB J 2002). The aim of this study was to assess the value of classical conditioning to MX for the treatment of MS, in order to save on drug dose and thus extend overall treatment duration. We designed a single-blind, placebo-controlled trial involving nine MS patients who are treated with MX 12mg/m2. For conditioning, patients received MX on the first day of treatment together with a novel, distinctively flavored, blue-colored drink, the CS. After 3 months patients were re-exposed to the CS, but now paired with an identical looking (blue color) placebo infusion. Two weeks after CS re-exposition patients received MX again paired with the CS to ensure that patients received the appropriate treatment. Blood was drawn before and one hour after each infusion and again two weeks later for the determination of immunological parameters. We analyzed differenzial blood counts and lymphocyte subpopulations on whole blood by flow cytometry. Peripheral blood mononuclear cells were separated and cell death, cytokine production as well as T cell proliferation of CD4+ and CD8+ cells to polyclonal stimuli were analyzed. MX treatment resulted in a significant reduction of leukocyte numbers in peripheral blood, primarily affecting neutrophils and B cells, two weeks after MX administration. IFN-g production and T cell proliferation upon stimulation with anti-CD3 and superantigen in vitro were transiently decreased after MX administration. This immunomodulatory effect by MX was not observed when patients received the CS and placebo alone, probably due to an incomplete conditioning. Complete analysis of immunological parameters will be presented.