Control of IgE responses. II. Isotype specific suppression of peak hapten specific IgE antibody forming cell responses in BPO-KLH sensitized mice after oral administration of muramyldipeptide or murabutide.
Muramyldipeptide (MDP) and murabutide (MB), a pyrogen free derivative of MDP, suppressed BPO specific IgE antibody forming cell (AFC) responses in vivo. To induce IgE responses, BALB/c mice were injected intraperitoneally (i.p.) with BPO-KLH (10 micrograms) in alum on days 0 and 21, or on days 0, 21 and 42. On day 44, mice were fed (gavage) or injected subcutaneously (s.c.) with MDP or MB (0.1-500 mg/kg). Mice were killed on days 45-70, and the numbers of BPO specific IgM, IgG1, IgE, and IgA antibody forming cells (AFC) in lymphoid organs determined in ELISPOT assay. With either immunization schedule, oral treatment with MDP or MB on day 44 suppressed BPO specific IgE AFC responses within 48 h (65-100%). With both molecules, the suppression was IgE isotype specific, dose dependent and transient. The suppression was also route specific since it was obtained only when MDP or MB was given by gavage, and not when injected s.c. These results show that peak antigen specific IgE responses can be suppressed in vivo, in isotype specific fashion, by a clearly defined class of molecules, one of which, MB, is a candidate for clinical studies in man. Pharmacologic agents of this type may be suitable for use in the therapeutic or prophylactic suppression of IgE and, hence, in the therapy of IgE mediated diseases such as allergic rhinitis, asthma, and other atopic diseases.