Selective immunosuppression following exposure to a novel anthraquinone, 1,4-bis[(2-aminoethyl)amino]-5,8-dihydroxy-9,10-anthracenedione dihydrochloride (AEAD).
The immune response of murine splenic lymphocytes was characterized following both in vivo and in vitro exposure to the novel and highly-substituted anthraquinone AEAD. Gross indicators of toxicity such as changes in body weight, lymphoid organ weights or lymphoid organ cellularity were unaffected. Similarly, the antibody plaque-forming cell response and natural killer cell function were unaltered. The most consistent effect noted was the selective suppression of the cytotoxic T-lymphocyte (CTL) response, which persisted for an extended period of time following in vivo exposure at concentrations of 0.75-3.0 micrograms/g. In contrast to the CTL suppression induced by the polycyclic aromatic hydrocarbon 7,12-dimethylbenz[a]-anthracene, AEAD-induced CTL suppression could not be restored by addition of exogenous interleukin-2. Studies are currently underway to further characterize AEAD-induced immunosuppression at the cellular and molecular levels.
House
R V
RV
Department of Cellular and Molecular Toxicology, Chemical Industry Institute of Toxicology, Research Triangle Park 27709.
Lauer
L D
LD
Thurmond
L M
LM
Cornacoff
J B
JB
Dean
J H
JH
D000818:Animals; D000917:Antibody Formation / Q000187:drug effects; D005260:Female; D007165:Immunosuppression Therapy; D066298:In Vitro Techniques; D007274:Injections, Intraperitoneal; D007694:Killer Cells, Natural / Q000187:drug effects; D051379:Mice; D008942:Mitoxantrone / Q000031:analogs & derivatives* / Q000494:pharmacology; D009929:Organ Size; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects* / Q000276:immunology; D013997:Time Factors; D010948:Viral Plaque Assay
C043485:CL 232468; D008942:Mitoxantrone