Pentoxifylline, a phosphodiesterase inhibitor, induces immune deviation in patients with multiple sclerosis

• Published in: Journal of neuroimmunology 1996-02, Vol.64 (2), p.193-200
• Main Authors: Rieckmann, Peter, Weber, Frank, Günther, Astrid, Martin, Stephan, Bitsch, Andreas, Broocks, Andreas, Kitze, Bernd, Weber, Thomas, Börner, Thomas, Poser, Sigrid
• Format: Article
• Language: English
• Subjects: Autoimmune Diseases - drug therapy; Autoimmune Diseases - immunology; Base Sequence; Cytokines; Cytokines - drug effects; Humans; Intercellular Adhesion Molecule-1 - drug effects; Lymphocyte Activation - drug effects; Molecular Probes - genetics; Molecular Sequence Data; Monocytes - drug effects; Multiple sclerosis; Multiple Sclerosis - drug therapy; Multiple Sclerosis - immunology; Pentoxifylline; Pentoxifylline - pharmacology; Pentoxifylline - therapeutic use; Phosphodiesterase Inhibitors - pharmacology; Phosphodiesterase Inhibitors - therapeutic use; Receptors, Interleukin-2 - drug effects; RNA, Messenger - drug effects; Single-Blind Method; T-Lymphocytes - drug effects; T-Lymphocytes, Helper-Inducer - drug effects; Treatment; Tumor necrosis faclor-α
• ISSN: 0165-5728; 1872-8421
• DOI: 10.1016/0165-5728(95)00176-X

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.