title: Pentoxifylline, a phosphodiesterase inhibitor, induces immune deviation in patients with multiple sclerosis.
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-alpha) and interferon-gamma (IFN-gamma), this drug was used in mitogen and antigen-stimulated lymphocyte cultures as well as in patients with multiple sclerosis. PTX significantly decreased TNF-alpha 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 alpha-chain) and CD54 (intercellular adhesion molecule-1; ICAM-1) expression. Increasing doses of PTX significantly reduced TNF-alpha 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.
authors.affiliation: Laboratory of Neurobiology, Department of Neurology, Georg-August-University Göttingen, Germany.
authors.forename: P
authors.initials: P
authors.lastname: Rieckmann
authors.forename: F
authors.initials: F
authors.lastname: Weber
authors.forename: A
authors.initials: A
authors.lastname: Günther
authors.forename: S
authors.initials: S
authors.lastname: Martin
authors.forename: A
authors.initials: A
authors.lastname: Bitsch
authors.forename: A
authors.initials: A
authors.lastname: Broocks
authors.forename: B
authors.initials: B
authors.lastname: Kitze
authors.forename: T
authors.initials: T
authors.lastname: Weber
authors.forename: T
authors.initials: T
authors.lastname: Börner
authors.forename: S
authors.initials: S
authors.lastname: Poser
mesh_terms: D001327:Autoimmune Diseases / Q000188:drug therapy* / Q000276:immunology*; D001483:Base Sequence; D016207:Cytokines / Q000187:drug effects; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000187:drug effects; D008213:Lymphocyte Activation / Q000187:drug effects; D015335:Molecular Probes / Q000235:genetics; D008969:Molecular Sequence Data; D009000:Monocytes / Q000187:drug effects; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000276:immunology*; D010431:Pentoxifylline / Q000494:pharmacology / Q000627:therapeutic use*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000187:drug effects; D015375:Receptors, Interleukin-2 / Q000187:drug effects; D016037:Single-Blind Method; D013601:T-Lymphocytes / Q000187:drug effects; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects
chemical_list: D016207:Cytokines; D015335:Molecular Probes; D010726:Phosphodiesterase Inhibitors; D012333:RNA, Messenger; D015375:Receptors, Interleukin-2; D018799:Intercellular Adhesion Molecule-1; D010431:Pentoxifylline