Pentoxifylline, a phosphodiesterase inhibitor, induces immune deviation in patients with multiple sclerosis |
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Authors: | Peter Rieckmann Frank Weber Astrid Günther Stephan Martin Andreas Bitsch Andreas Broocks Bernd Kitze Thomas Weber Thomas Börner Sigrid Poser |
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Institution: | aLaboratory of Neurobiology, Departments of Neurology and Psychiatry, Georg-August-University Göttingen, Göttingen, Germany;bClinical Department, Diabetes Research Institute, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany |
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Abstract: | The outcome of immune responses can be predicted by the lymphokine production pattern of the participating cells. Cytokines of the T helper type 1 (Th1) cells mediate inflammatory responses and delayed-type hypersensitivity (DTH), whereas Th2-like T cells predominantly produce cytokines, which stimulate antibody production by B cells. Immunoregulatory therapy of autoimmune diseases with unknown antigens may be achieved by inhibiting the production of inflammatory cytokines and induction of protective cytokines of Th2-like T cells. To determine the immunoregulatory capacity of the phosphodiesterase inhibitor pentoxifylline (PTX), which is known to suppress the production of tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ), this drug was used in mitogen and antigen-stimulated lymphocyte cultures as well as in patients with multiple sclerosis. PTX significantly decreased TNF-α and interleukin-12 (IL-12), whereas it increased IL-4 and IL-10 production. In addition, PTX inhibited cell proliferation, which was associated with a marked reduction in CD25 (IL-2 receptor α-chain) and CDS4 (intercellular adhesion molecule-1; ICAM-1) expression. Increasing doses of PTX significantly reduced TNF-α and IL-12 mRNA expression of blood mononuclear cells, but increased IL-4 and IL-10 expression in eight patients with relapsing-remitting multiple sclerosis. These results indicate that PTX modulates immune reactions favouring a Th2-like response and may therefore be useful for the treatment of autoimmune diseases with a dominant Th1-like T cell response. |
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Keywords: | Multiple sclerosis Cytokines Pentoxifylline Tumor necrosis faclor-α Treatment |
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