The effects of phosphodiesterase inhibitors (PDEIs) on interleukin (IL)-12 production by microglia, antigen-presenting cells in the central nervous system (C NS), were examined to learn how they affect T cell differentiatio n in the C NS. PDEIs significantly suppressed the microglial IL-12 production, as determined by reverse transcriptase-po lymerase chain reaction for IL-12 p35 and p40 mRNA expression and by an ELISA specific for IL-12 functional hetero dimer, p70. In addition, the PDEI ibudilast also suppressed interferon-g, but not IL-4 or IL-10, production by myelin oligodendro cyte glycoprotein (MO G)-specific T cells reactivated with MO G in the presence of microglia. Thus, PDEIs may also suppress differentiatio n of T helper 1 (Th1) in the C NS. PDEIs can be of use for future therapeutic strategy to treat Th1-mediated diseases, such as multiple sclerosis.