Murine retroviral disease-enhancing effects of a pyrimidinone immunomodulator.
(B10.A x A/WySn)F1 mice, infected with the Friend virus (FV) complex, were used as a predictive therapeutic model for AIDS. These infected mice exhibit many of the viral and immunologic manifestations of AIDS. Bropirimine (2-amino-5-bromo-6-phenyl-4[3H]pyrimidinone, ABPP) is an immunomodulating compound which has been shown to inhibit other viral infections. Oral (per os treatment) dosages of ABPP ranging from 50 to 400 mg/kg/day for 3 days resulted in increased numbers of infectious centers in the infected mice and increased splenomegaly and percentage of Ig+ (B cells) in spleens of infected and uninfected mice. Decreased percentages of total Thy-1.2+ (total T) cells and L3T4+ (T-helper) cells were seen in both uninfected and infected mice and a slightly decreased percentage of Ly-2+ (T-suppressor/cytotoxic) cells was observed in spleens of the infected mice. No effect on Ly2+ cells in spleens of uninfected mice was found. Intraperitoneal injection, single or multiple, of 20-200 mg/kg ABPP prior to FV injection resulted in increased spleen weights but had no effect on numbers of infectious centers in the spleens or on FV antibody titers in the plasma. Intraperitoneal treatment of uninfected mice with ABPP resulted in slight or no changes in percentages of Thy-1.2+, L3T4+ and Ly-2+ cells. Mice receiving multiple exposures of ABPP had an increase in percentage of splenic B cells and a depressed response to the T cell mitogen PHA. Treatment with ABPP induced the production of interferon (IFN); however, a state of hyporesponsive IFN production was seen following multiple administrations of ABPP. These data suggest that the immunomodulator ABPP may have an enhancing effect on this retroviral disease.
Warren
R P
RP
AIDS Research Program, Utah State University, Logan 84322-6895.
Morrey
J D
JD
Burger
R A
RA
Okleberry
K M
KM
Sidwell
R W
RW
D000163:Acquired Immunodeficiency Syndrome; D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000494:pharmacology*; D000284:Administration, Oral; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology; D003596:Cytosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004195:Disease Models, Animal; D005622:Friend murine leukemia virus / Q000187:drug effects*; D007274:Injections, Intraperitoneal; D007369:Interferon Inducers / Q000008:administration & dosage / Q000494:pharmacology; D007942:Leukemia, Experimental / Q000188:drug therapy*; D051379:Mice; D008815:Mice, Inbred Strains
D000276:Adjuvants, Immunologic; D000970:Antineoplastic Agents; D007369:Interferon Inducers; D003596:Cytosine; C033560:bropirimine