SUPPRESSION OF HUMAN-IMMUNOGLOBULIN-E ANTIBODY-PRODUCTION BY A NEW NAPHTHALENE DERIVATIVE

A new naphthalene derivative, (E)-2-(7-(2-naphthyl)-6-heptenamide)benz acid (TEI-8364) was assessed for its effect on interleukin (IL)-4- an d anti-CD40 monoclonal antibody-induced immunoglobulin E (IgE) product ion 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 add ition, TEI-8364, at a concentration of 10 mu M, completely inhibited I L-4- and anti-CD40-induced IgE production by purified tonsillar B lymp hocytes, 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 ant ibody to a T cell-dependent antigen by PBMC from an immunized voluntee r, cultured in the presence of antigen. Furthermore, TEI-8364 at a dos e of 1 mg/mouse/day selectively inhibited IgE production by severe com bined 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 usefu l in the treatment of IgE-mediated allergic disorders.