Control of IgE responses. V. Oral administration of a synthetic derivative of the inner bacterial cell wall (SDZ 280.636) to sensitized mice induces isotype specific suppression of peak hapten specific IgE antibody forming cell responses, serum IgE levels and immediate hypersensitivity responses.
SDZ 280.636, a nontoxic diacyl glycerol derivative of muramyl dipeptide (MDP), a component of the inner bacterial cell wall, which is suitable for use in man, suppressed hapten specific IgE antibody forming cell (AFC) responses in spleen, serum levels of hapten specific IgE and hapten specific immediate hypersensitivity (i.h.) responses in skin, when fed to mice at the peak of a hapten specific IgE AFC response. In addition, serum levels of IL-6 appeared increased while IFN gamma was decreased. To induce these IgE responses, BALB/c mice were injected i.p. with BPO-KLH (benzylpenicilloyl-keyhole limpet hemocyanin) (10 micrograms) in aluminum hydroxide gel (alum) on days 0, 21 and 42. Mice were fed (gavage) with either MDP or SDZ 280.636 (1.0 or 10 mg/kg) on day 44, or on days 44, 46 and 48, and killed on days 46 or 50. Numbers of BPO specific AFC in spleen, and serum levels of BPO specific immunoglobulins (IgG1, IgE and IgA) were determined (ELISPOT assay, ELISA). In addition, BPO specific IH responses were measured in these animals. Mice were injected in the right pinna with BPO-BSA (0.1 microgram) and in the left pinna with an equal volume of saline (0.05 ml). At 2 hr, pinnae were measured using a micrometer caliper. We found that 1 feeding with either MDP or SDZ 280.636 abrogated IgE AFC responses and dramatically suppressed serum levels of IgE, both in isotype specific fashion, and suppressed IH responses (> 50%). 3 feedings with SDZ 280.636 also abrogated IgE AFC responses and further decreased serum levels of IgE. In contrast to SDZ 280.636, 3 treatments with MDP had opposite effects in that IgE AFC responses and serum levels of IgE dramatically increased. A single treatment with SDZ 280.636 appeared to increase serum levels of IL-6 up to three fold, while IFN gamma levels decreased. Our data suggest that SDZ 280.636 may be useful in the therapeutic and prophylactic management of human atopic disease such as allergic rhinitis, asthma, and other atopic diseases.
Auci
D L
DL
Department of Pathology, State University of New York Health Science Center at Brooklyn.
Kleiner
G I
GI
Chice
S M
SM
Athanassiades
T J
TJ
Dukor
P
P
Durkin
H G
HG
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000494:pharmacology; D000284:Administration, Oral; D000818:Animals; D018926:Anti-Allergic Agents / Q000494:pharmacology*; D000917:Antibody Formation; D044482:Benzeneacetamides; D004151:Dipeptides / Q000494:pharmacology*; D006241:Haptens / Q000276:immunology*; D006969:Hypersensitivity, Immediate / Q000276:immunology*; D007070:Immunoglobulin A / Q000276:immunology; D007073:Immunoglobulin E / Q000097:blood* / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D007132:Immunoglobulin Isotypes / Q000097:blood* / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010400:Penicillin G / Q000031:analogs & derivatives* / Q000276:immunology; D051381:Rats
D018926:Anti-Allergic Agents; D044482:Benzeneacetamides; D004151:Dipeptides; D006241:Haptens; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007132:Immunoglobulin Isotypes; C106787:SDZ 280.636; C015026:benzylpenicilloyl G; D007073:Immunoglobulin E; D000119:Acetylmuramyl-Alanyl-Isoglutamine; D010400:Penicillin G