Suppression of human immunoglobulin E antibody production by a new naphthalene derivative.
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.
Pharmaceutical Discovery Research Laboratory, Teijin Institute for Biomedical Research, Tokyo, Japan.
Y
Y
Uejima
K
K
Takahashi
K
K
Komoriya
S
S
Kurozumi
H D
HD
Ochs
D000328:Adult; D000577:Amides / Q000494:pharmacology*; D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000637:transplantation; D001565:Benzoates / Q000494:pharmacology*; D006801:Humans; D007073:Immunoglobulin E / Q000096:biosynthesis*; D007074:Immunoglobulin G / Q000096:biosynthesis; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D066298:In Vitro Techniques; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D051379:Mice; D016513:Mice, SCID; D014183:Transplantation, Heterologous
D000577:Amides; D001565:Benzoates; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; C097356:TEI 8364; D007073:Immunoglobulin E