CONTROL OF IGE RESPONSES .2. ISOTYPE-SPECIFIC SUPPRESSION OF PEAK HAPTEN-SPECIFIC IGE ANTIBODY-FORMING CELL RESPONSES IN BPO-KLH SENSITIZEDMICE 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) respon ses in vivo. To induce IgE responses, BALB/c mice were injected intrap eritoneally (i.p.) with BPO-KLH (10 mug) in alum on days 0 and 21, or on days 0, 21 and 42. On day 44, mice were fed (gavage) or injected su bcutaneously (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 no t 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 Ig E and, hence, in the therapy of IgE mediated diseases such as allergic rhinitis, asthma, and other atopic diseases.