Interleukin‐12 regulates natural killer cell‐dependent Propionibacterium acnes‐primed, lipopolysaccharide‐induced liver injury
- 9 August 2007
- journal article
- Published by Wiley in Hepatology Research
- Vol. 38 (2), 183-193
- https://doi.org/10.1111/j.1872-034x.2007.00214.x
Abstract
Interleukin (IL)-12, produced primarily by macrophage/monocytes, modulates mature T and natural killer (NK) cell functions, including cytotoxicity and cytokine production. To determine the role of IL-12 in Propionibacterium acnes (P. acnes)-primed, lipopolysaccharide (LPS)-induced liver injury, mice were injected with an anti-IL-12 monoclonal antibody (mAb) 1 and 2 days before P. acnes injection (day 0) or 5 and 6 days before LPS challenge (day 7). The survival rates, plasma cytokine levels, and liver mononuclear cell phenotypes were evaluated for the mice treated with and without anti-IL-12 mAb. The observed mortality with P. acnes-primed, LPS-induced liver injury in C57BL/6 (B6) mice was 100%, but was reduced to 0% in interferon (IFN)-gamma receptor-deficient mice and B6 mice treated with anti-IL-12 mAb on 1 and 2 days before P. acnes exposure (day 0). The plasma IFN-gamma levels weresignificantly lower (P < 0.05), and significantly less ( approximately 90% reduction) hepatic infiltrating mononuclear and NK1.1 cells were also found in the IL-12 mAb-treated, P. acnes-primed mice. The plasma cytokine levels after LPS challenge and in vitro cytokine release by liver mononuclear cells were significantly lower (P < 0.05) in the mice treated with anti-IL-12 mAb prior to P. acnes exposure. The in vivo administration of anti-NK1.1 mAb also improved survival in this liver injury model. IL-12-regulated IFN-gamma production is crucial during the priming phase by P. acnes, but not at the time of the subsequent LPS challenge. NK1.1(+)CD3(-)CD4(-) NK or NK1.1(+)CD3(+)CD4(-) NKT cells are important in this model of liver injury.Keywords
This publication has 53 references indexed in Scilit:
- Selective induction of NK cell proliferation and cytotoxicity by activated NKT cellsEuropean Journal of Immunology, 2000
- Rapid Death and Regeneration of NKT Cells in Anti-CD3ε- or IL-12-Treated MiceImmunity, 1998
- THE INTERLEUKIN-12/INTERLEUKIN-12-RECEPTOR SYSTEM: Role in Normal and Pathologic Immune ResponsesAnnual Review of Immunology, 1998
- MOUSE CD1-SPECIFIC NK1 T CELLS: Development, Specificity, and FunctionAnnual Review of Immunology, 1997
- Strange brew: T cells in the liverImmunology Today, 1996
- Interleukin‐12 is required for interferon‐γ production and lethality in lipopolysaccharide‐induced shock in miceEuropean Journal of Immunology, 1995
- Immune Response in Mice that Lack the Interferon-γ ReceptorScience, 1993
- Multiple Defects of Immune Cell Function in Mice with Disrupted Interferon-γ GenesScience, 1993
- Natural killer cell stimulatory factor (NKSF) or interleukin-12 is a key regulator of immune response and inflammationProgress in Growth Factor Research, 1992
- Characterization of a monoclonal antibody directed against mouse macrophage and lymphocyte Fc receptors.The Journal of Experimental Medicine, 1979