In vivo treatment with interleukin 12 protects mice from immune abnormalities observed during murine acquired immunodeficiency syndrome (MAIDS).
Lymphoproliferation, chronic B cell activation resulting in hypergammaglobulinemia, and profound immunodeficiency are prominent features of a retrovirus-induced syndrome designated murine acquired immunodeficiency syndrome (MAIDS). In vivo treatment of infected mice with recombinant interleukin 12 (IL-12) beginning at the time of infection or up to 9 wk after virus inoculation markedly inhibited the development of splenomegaly and lymphadenopathy, as well as B cell activation and Ig secretion. Treatment with IL-12 also had major effects in preventing induction of several immune defects including impaired production of interferon gamma (IFN-gamma) and IL-2 and depressed proliferative responses to various stimuli. The therapeutic effects of IL-12 on the immune system of mice with MAIDS were also associated with reduced expression of the retrovirus that causes this disease (BM5def), with lesser effects on expression of ecotropic MuLV. IL-12 treatment was not effective in IFN-gamma knockout mice or in infected mice treated simultaneously with IL-12 and anti-IFN-gamma. These results demonstrate that induction and progression of MAIDS are antagonized by IL-12 through high-level expression of IFN-gamma and may provide an experimental basis for developing treatments of retrovirus-induced immune disorders with similar immunopathogenic mechanisms.
Section of Immunobiology and Cell Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892.
R T
RT
Gazzinelli
N A
NA
Giese
H C
HC
Morse
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D001483:Base Sequence; D017931:DNA Primers; D005260:Female; D005434:Flow Cytometry; D007041:Hypoxanthine Phosphoribosyltransferase / Q000096:biosynthesis; D007371:Interferon-gamma / Q000276:immunology; D018664:Interleukin-12 / Q000494:pharmacology / Q000627:therapeutic use*; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D016183:Murine Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000503:physiopathology / Q000628:therapy; D009929:Organ Size / Q000187:drug effects; D016133:Polymerase Chain Reaction; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use; D013163:Splenomegaly / Q000517:prevention & control; D013997:Time Factors
D000911:Antibodies, Monoclonal; D017931:DNA Primers; D011994:Recombinant Proteins; D018664:Interleukin-12; D007371:Interferon-gamma; D007041:Hypoxanthine Phosphoribosyltransferase