SUPPRESSION OF IGE ANTIBODY-RESPONSE IN MICE BY A NAPHTHALENE DERIVATIVE, TEI-6472

In the present report, we investigated suppressive effects of a naphth alene derivative, -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 T NP-keyhole limpet hemocyanin (KLH)-primed murine spleen cells was supp ressed 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 suppresse d under the same conditions. Proliferative responses of BALB/c spleen cells stimulated by lipopolysaccharide, concanavalin A or allogeneic s pleen cells were not inhibited by TEI-6472 at 10(-6) - 10(-5) M. Inter leukin 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/da y TEI-6472 was administered s.c. for 5 consecutive days starting from one day before the first and the second immunization, secondary anti-T NP 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 re sults suggest that, under appropriate conditions, TEI-6472 can suppres s IgE responses more preferentially both in vitro and in vivo.