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...

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Bibliographic Details
Published in:Immunopharmacology 1995-08, Vol.30 (2), p.167-176
Main Authors: Uejima, Yasuhide, Takahashi, Katsushi, Komoriya, Keiji, Kurozumi, Seizi, Ochs, Hans D.
Format: Article
Language:English
Subjects:
Adult
Amides - pharmacology
Animals
B-Lymphocytes - drug effects
B-Lymphocytes - immunology
B-Lymphocytes - transplantation
Benzoates - pharmacology
Biological and medical sciences
CD40
Humans
Immunoglobulin E
Immunoglobulin E - biosynthesis
Immunoglobulin G - biosynthesis
Immunomodulators
Immunosuppressive Agents - pharmacology
In Vitro Techniques
Interleukin-10
Interleukin-4
Lymphocyte Activation - drug effects
Male
Medical sciences
Mice
Mice, SCID
Naphthalene derivative
Pharmacology. Drug treatments
Severe combined immunodeficiency (SCID) mouse
Transplantation, Heterologous
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Summary: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 μM, 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.
ISSN:0162-3109
DOI:10.1016/0162-3109(95)00021-K