Suppression of IgE production by IPD-1151T (suplatast tosilate), a new dimethylsulfonium agent: (1). Regulation of murine IgE response.
The effect of IPD-1151T, a new dimethylsulfonium compound, on the IgE response was investigated in the mouse system. The oral administration of IPD-1151T to immunized BALB/c mice suppressed the primary IgE antibody response and depressed the elevation of serum IgE levels, whereas the same treatment did not affect the IgG antibody response. The enhanced expression of low-affinity IgE receptor (Fc epsilon RII/CD23) on the spleen cells of immunized mice was also inhibited by IPD-1151T administration. It was further demonstrated from the adoptive transfer experiment that IPD-1151T, administered to hapten-primed B cell donors, but not to carrier-primed T cell donors, exerted its suppressive influence on the hapten-specific secondary IgE antibody response in irradiated syngeneic recipients. Interestingly, IPD-1151T concentration-dependently inhibited the production of interleukin 4 (IL-4) by D10G4.1, known to be a typical Th2 clone. However, IPD-1151T did not suppress the production of IgE and IgG1 by normal splenic B cells stimulated with lipopolysaccharide and IL-4. Moreover, IL-4-induced expression of Fc epsilon RII on normal spleen cells was not inhibited by the agent. These results strongly suggest that the IgE-suppressive activity of IPD-1151T is most likely due to the inhibition of IL-4 production at the T cell level.
Clinical Research Center for Allergy, National Sagamihara Hospital, Kanagawa, Japan.
Y
Y
Yanagihara
M
M
Kiniwa
K
K
Ikizawa
H
H
Yamaya
T
T
Shida
N
N
Matsuura
A
A
Koda
D000284:Administration, Oral; D000818:Animals; D000911:Antibodies, Monoclonal; D001190:Arylsulfonates / Q000008:administration & dosage / Q000494:pharmacology*; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D006633:Histamine Antagonists / Q000494:pharmacology*; D007073:Immunoglobulin E / Q000096:biosynthesis*; D007074:Immunoglobulin G / Q000097:blood; D015847:Interleukin-4 / Q000096:biosynthesis / Q000276:immunology; D008297:Male; D051379:Mice; D008806:Mice, Inbred AKR; D008807:Mice, Inbred BALB C; D051381:Rats; D017208:Rats, Wistar; D017455:Receptors, IgE / Q000096:biosynthesis; D013452:Sulfonium Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology
D000911:Antibodies, Monoclonal; D001190:Arylsulfonates; D006633:Histamine Antagonists; D007074:Immunoglobulin G; D017455:Receptors, IgE; D013452:Sulfonium Compounds; D015847:Interleukin-4; D007073:Immunoglobulin E; C073028:suplatast tosilate