We report a novel synthetic compound
JTP-27536 [(+)-1,3-dihydroxy-2-hydroxymethylpropyl-2-
ammonium 2-[(R)-3-cyclohexyl-1-phenylpropyl]-1,3-dioxo-2,3-dihydro-1H-
isoindole-5-carboxylate monohydrate] as an inhibitor of
immunoglobulins (Igs) and
interleukin (IL)-5 production in vitro and in vivo.
JTP-27536 inhibited
IgE production in mouse and human B cells with IC50 values of 2.5 and 2.1 microM, respectively, and the inhibition was stronger than that on
IgG1 and
IgM production (IC50 > 10 microM).
JTP-27536 also inhibited
IL-5 production in mouse splenocytes and human peripheral blood mononuclear cells with IC50 values of 3.3 and 1.3 microM, respectively, without affecting mouse
interferon (IFN)-gamma,
IL-2,
IL-4,
IL-10, or human
IL-4 production. In contrast,
prednisolone not only inhibited mouse
IgE production but also mouse IFN-gamma,
IL-2,
IL-4, and
IL-10 and human
IL-4 and
IL-5 production in vitro. The effect of
suplatast tosilate, a Th2
cytokine inhibitor, on antibody and
cytokine production was less potent than that of
JTP-27536. In vivo animal experiments using dinitrophenylated ascaris-sensitized mice and 2,4,6-trinitro-1-chrolobenzene-induced chronic
dermatitis mice showed that
JTP-27536 was more potent than
suplatast tosilate and comparable with
prednisolone in inhibiting ear swelling,
antigen-specific
IgE and
IL-5 production, and cell infiltrations into the inflamed tissue. These results indicate that
JTP-27536 is an inhibitor of Igs, in particular
IgE, and of
IL-5, which has
antiallergic properties in mouse
dermatitis model, and suggest that an inhibitor of Igs and
IL-5 like
JTP-27536 may be useful as a
drug for the treatment of allergic diseases.