In vivo treatment with interleukin 12 protects mice from immune abnormalities observed during murine acquired immunodeficiency syndrome (MAIDS).

Abstract

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.

• Authors: R T Gazzinelli, N A Giese, H C Morse 3rd
• Journal: The Journal of experimental medicine (J Exp Med) Vol. 180 Issue 6 Pg. 2199-208 (Dec 01 1994) ISSN: 0022-1007 [Print] United States
• PMID: 7964495 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antibodies, Monoclonal
• DNA Primers
• Recombinant Proteins
• Interleukin-12
• Interferon-gamma
• Hypoxanthine Phosphoribosyltransferase

Topics

• Animals
• Antibodies, Monoclonal (pharmacology)
• B-Lymphocytes (drug effects, immunology)
• Base Sequence
• DNA Primers
• Female
• Flow Cytometry
• Hypoxanthine Phosphoribosyltransferase (biosynthesis)
• Interferon-gamma (immunology)
• Interleukin-12 (pharmacology, therapeutic use)
• Lymphocyte Activation (drug effects)
• Mice
• Mice, Inbred C57BL
• Molecular Sequence Data
• Murine Acquired Immunodeficiency Syndrome (immunology, physiopathology, therapy)
• Organ Size (drug effects)
• Polymerase Chain Reaction
• Recombinant Proteins (pharmacology, therapeutic use)
• Splenomegaly (prevention & control)
• Time Factors