Treatment of the murine, retrovirus-induced lymphoproliferative immunodeficiency disease (LP-BM5) in C57BL/10 mice with the immunomodulator Imexon.
Imexon (4-imino-1, 3-diazabicyclo-(3.1.0)-hexan-2-one) a cyanoaziridine compound was studied in the treatment of the murine retrovirus-induced immunodeficiency disease model of AIDS (LP-BM5, MAIDS). Imexon, in dose-dependent fashion, partially prevented the development of hypergammaglobulinemia and splenomegaly, and partially prevented the decline in the phytohemagglutinin-induced proliferative response of spleen lymphocytes when started 1 or 15 days after virus inoculation. There was a statistically significant reduction in these disease-associated manifestations. When animals were treated starting 78 or 92 days after virus inoculation, lymphadenopathy was completely abrogated and survival was significantly prolonged in a dose-responsive manner. Since Imexon and other cyanoaziridine compounds have been safely administered to humans, we suggest that this class of compounds be further investigated in both large animal models of HIV infection and in patients with HIV-induced disease.
Funk
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Section of Hematology and Oncology, Arizona Cancer Center, Tucson 85724.
Eisman
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Hersh
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EM
D000818:Animals; D000998:Antiviral Agents / Q000627:therapeutic use*; D005260:Female; D006588:Hexanones / Q000627:therapeutic use*; D007075:Immunoglobulin M / Q000097:blood; D051379:Mice; D008810:Mice, Inbred C57BL; D016183:Murine Acquired Immunodeficiency Syndrome / Q000188:drug therapy* / Q000276:immunology; D012190:Retroviridae
D000998:Antiviral Agents; D006588:Hexanones; D007075:Immunoglobulin M; C014919:4-imino-1,3-diazabicyclo(3.1.0)hexan-2-one