Recombinant interleukin-12 enhances resistance of mice to Listeria monocytogenes infection.
The effect of recombinant murine IL-12 (rIL-12) or anti-IL-12 antibody administration on resistance to murine listeriosis was investigated. Mice given a single 0.5 micrograms dose of rIL-12 had 1.5 log10 fewer listeriae in their spleens and livers as compared with control infected mice 3 days after L. monocytogenes challenge. Conversely, administration of anti-IL-12 IgG caused an equivalent increase in the cfu of L. monocytogenes recovered from the spleens and livers as compared to control mice. This is the first report of such a protective effect from a single dose of rIL-12. Treatment of uninfected mice with rIL-12 induced IFN-gamma mRNA production in their livers. Infection of mice with L. monocytogenes caused a similar increase in IFN-gamma mRNA levels that was not increased further by concurrent treatment with rIL-12. Treatment of mice with an anti-IFN-gamma MAb eliminated the protective effect of IL-12 on Listeria infection. Expression of TNF-alpha, IL-10 and IL-12p40 mRNA in L. monocytogenes-infected mice were not significantly altered by administration of either anti-IL-12 IgG or rIL-12. rIL-12 administration was associated with increased serum AST levels, a measure of liver damage, 1 day after treatment in L. monocytogenes-infected mice. In addition, rIL-12 administration was associated with the increased presence of small inflammatory foci and necrotic hepatocytes in both infected and uninfected mice, suggesting a proinflammatory role for IL-12 in the liver.
Wagner
R D
RD
Department of Pathobiological Sciences, University of Wisconsin School of Veterinary Medicine, Madison 53706.
Steinberg
H
H
Brown
J F
JF
Czuprynski
C J
CJ
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D001219:Aspartate Aminotransferases / Q000097:blood; D001483:Base Sequence; D007113:Immunity, Innate; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D016753:Interleukin-10 / Q000096:biosynthesis; D018664:Interleukin-12 / Q000276:immunology / Q000627:therapeutic use*; D008089:Listeria monocytogenes; D008088:Listeriosis / Q000276:immunology* / Q000378:metabolism / Q000628:therapy; D008099:Liver / Q000378:metabolism / Q000382:microbiology; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000276:immunology / Q000627:therapeutic use; D013154:Spleen / Q000382:microbiology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D000911:Antibodies, Monoclonal; D012333:RNA, Messenger; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D018664:Interleukin-12; D007371:Interferon-gamma; D001219:Aspartate Aminotransferases