A new
naphthalene derivative, (E)-2-(7-(2-naphthyl)-6-heptenamide)benzoic
acid (TEI-8364) was assessed for its effect on
interleukin (IL)-4- and anti-CD40
monoclonal antibody-induced
immunoglobulin E (
IgE) production by cultured human lymphocytes.
TEI-8364 preferentially suppressed the production of
IgE by peripheral blood mononuclear cells (PBMC) in a dose-dependent manner, without inhibiting PBMC proliferation. In addition,
TEI-8364, at a concentration of 10 microM, completely inhibited IL-4- and anti-CD40-induced
IgE production by purified tonsillar B lymphocytes, suggesting that
TEI-8364 affects B cells by interfering with signals provided by
IL-4 or through CD40 and
IL-4.
TEI-8364 also had a profound inhibiting effect on the in vitro production of specific antibody to a T cell-dependent
antigen by PBMC from an immunized volunteer, cultured in the presence of
antigen. Furthermore,
TEI-8364 at a dose of 1 mg/mouse/day selectively inhibited
IgE production by
severe combined immunodeficiency mice engrafted with human PBMC, if the
drug was administered subcutaneously for five consecutive days. These findings suggest that
TEI-8364 is a potent therapeutic agent that may be useful in the treatment of
IgE-mediated allergic disorders.