Protective effect of cyclosporin A on immune abnormalities observed in the murine acquired immunodeficiency syndrome.
The murine leukemia viruses (MuLV) designated LP-BM5 induce an immunodeficiency disease in susceptible strains of mice with many features in common to human acquired immunodeficiency syndrome (AIDS), including lymphadenopathy and profound immunodeficiency associated with enhanced susceptibility to infection and terminal B cell lymphomas. The disease, termed murine AIDS (MAIDS), crucially depends on the presence of B cells and CD4+ T cells, suggesting that mutual activation of these two cell types is central in the pathogenesis of the immunodeficiency syndrome. Cyclosporin A (CsA), whose immunosuppressive effect is attributed mainly to inhibition of interleukin 2 and interferon-gamma expression, interferes in T-B cell interactions. Here we show that chronic treatment with CsA (40 or 60 mg/kg/day) before and after infection with LP-BM5 MuLV protects against the development of immunodeficiency disease as assessed by functional, serological and histopathological criteria. The protection was not complete, suggesting both CsA-sensitive and CsA-resistant components to the pathogenesis of this syndrome, and was found to be independent of ecotropic MuLV expression. These results underline immunopathological mechanisms in the progression of immune abnormalities in MAIDS that are susceptible to inhibition of CsA and may serve as an experimental basis for developing a treatment of the human disorder with immunomodulators.
Cerny
A
A
Clinique Médicale Thérapeutique, Hôpital Cantonal Universitaire, Switzerland.
Merino
R
R
Makino
M
M
Waldvogel
F A
FA
Morse
H C
HC
Izui
S
S
D000818:Animals; D000917:Antibody Formation / Q000187:drug effects; D003524:Cyclosporins / Q000627:therapeutic use*; D007074:Immunoglobulin G / Q000145:classification; D009052:Leukemia Virus, Murine / Q000187:drug effects; D007942:Leukemia, Experimental / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D016183:Murine Acquired Immunodeficiency Syndrome / Q000188:drug therapy* / Q000276:immunology
D003524:Cyclosporins; D007074:Immunoglobulin G