title: Phosphodiesterase inhibitors suppress IL-12 production with microglia and T helper 1 development.
abstract: The effects of phosphodiesterase inhibitors (PDEIs) on interleukin (IL)-12 production by microglia, antigen-presenting cells in the central nervous system (CNS), were examined to learn how they affect T cell differentiation in the CNS. PDEIs significantly suppressed the microglial IL-12 production, as determined by reverse transcriptase-polymerase chain reaction for IL-12 p35 and p40 mRNA expression and by an ELISA specific for IL-12 functional heterodimer, p70. In addition, the PDEI ibudilast also suppressed interferon-gamma, but not IL-4 or IL-10, production by myelin oligodendrocyte glycoprotein (MOG)-specific T cells reactivated with MOG in the presence of microglia. Thus, PDEIs may also suppress differentiation of T helper 1 (Th1) in the CNS. PDEIs can be of use for future therapeutic strategy to treat Th1-mediated diseases, such as multiple sclerosis.
authors.affiliation: Department of Neuroimmunology, Institute of Environmental Medicine, Nagoya University, Furo-cho, Chikusa, Nagoya 464-8601, Japan. suzumura@riem.nagoya-u.ac.jp
authors.forename: Akio
authors.initials: A
authors.lastname: Suzumura
authors.forename: Atsushi
authors.initials: A
authors.lastname: Ito
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Mizuno
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D000938:Antigen-Presenting Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D003994:Bucladesine / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D004357:Drug Synergism; D015870:Gene Expression / Q000187:drug effects / Q000276:immunology; D016899:Interferon-beta / Q000494:pharmacology; D018664:Interleukin-12 / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000166:cytology* / Q000187:drug effects / Q000276:immunology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology*; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology* / Q000187:drug effects / Q000276:immunology; D007212:Indolizines; D011720:Pyrazoles
chemical_list: D000276:Adjuvants, Immunologic; D003994:Bucladesine; D016899:Interferon-beta; D018664:Interleukin-12; D010726:Phosphodiesterase Inhibitors; D011725:Pyridines; C038366:ibudilast; D007212:Indolizines; D011720:Pyrazoles