Suppression of IgE antibody response in mice by a naphthalene derivative, TEI-6472.
In the present report, we investigated suppressive effects of a naphthalene derivative, (7E)-N-(2-carboxyphenyl)-8-(2-naphthyl)-5,6-trans-5,6-methano-7- octenamide L-lysine salt (TEI-6472), on in vitro and in vivo antigen-specific IgE response. Anti-trinitrophenyl (TNP) IgE response induced in vitro in TNP-keyhole limpet hemocyanin (KLH)-primed murine spleen cells was suppressed by about 60% in the presence of 10(-6) M TEI-6472. On the other hand, anti-TNP IgG1 and IgM response were not significantly suppressed under the same conditions. Proliferative responses of BALB/c spleen cells stimulated by lipopolysaccharide, concanavalin A or allogeneic spleen cells were not inhibited by TEI-6472 at 10(-6)-10(-5) M. Interleukin 4 production from helper T-cell clone, D10.G4.1 was suppressed only slightly (less than 20%) at 10(-6) M TEI-6472. This compound was also effective in suppressing secondary anti-TNP IgE response in mice that were immunized twice with TNP-KLH and alum. When 10-20 mg/kg/day TEI-6472 was administered s.c. for 5 consecutive days starting from one day before the first and the second immunization, secondary anti-TNP IgE response was inhibited most strongly (40-45%). Anti-TNP IgG1 response was also inhibited but to a smaller extent (20-24%), while anti-TNP IgM response was suppressed only slightly (0-15%). These results suggest that, under appropriate conditions, TEI-6472 can suppress IgE responses more preferentially both in vitro and in vivo.
Department of Biotechnology, Faculty of Engineering, Okayama University, Japan.
H
H
Ohmori
T
T
Kishimoto
M
M
Hikida
A
A
Hazato
S
S
Kurozumi
D000818:Animals; D000941:Antigens; D005260:Female; D006241:Haptens; D006433:Hemocyanins / Q000276:immunology; D007073:Immunoglobulin E / Q000096:biosynthesis*; D007074:Immunoglobulin G / Q000096:biosynthesis; D007075:Immunoglobulin M / Q000096:biosynthesis; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D066298:In Vitro Techniques; D015847:Interleukin-4 / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000187:drug effects; D007959:Lymphocyte Culture Test, Mixed; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D009281:Naphthalenes / Q000494:pharmacology*
D000941:Antigens; D006241:Haptens; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007166:Immunosuppressive Agents; D009281:Naphthalenes; C054401:trinitrophenyl keyhole limpet hemocyanin; C083345:TEI 6472; D015847:Interleukin-4; D007073:Immunoglobulin E; D006433:Hemocyanins