ArticleThe Journal of experimental medicine1998
Immune suppression by recombinant interleukin (rIL)-12 involves interferon gamma induction of nitric oxide synthase 2 (iNOS) activity: inhibitors of NO generation reveal the extent of rIL-12 vaccine adjuvant effect.
Article in The Journal of experimental medicine, 1998. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
33 citing papers in PubMed, 126 citations in OpenAlex.
- Fecal microbiota transplant overcomes resistance to anti-PD-1 therapy in melanoma patients.Science (New York, N.Y.) · 2021Trial
- Decoding the Myeloid-Derived Suppressor Cells in Lymphoid Malignancies.Journal of clinical medicine · 2021Review
- IFNγ: signalling, epigenetics and roles in immunity, metabolism, disease and cancer immunotherapy.Nature reviews. Immunology · 2018Review
- Myeloid-Derived Suppressor Cells as a Regulator of Immunity in Organ Transplantation.International journal of molecular sciences · 2018Review
- Host immune response to infection and cancer: unexpected commonalities.Cell host & microbe · 2014Review
- Can immunotherapy be useful as a "functional cure" for infection with Human Immunodeficiency Virus-1?Retrovirology · 2012Review
- Leishmania promotes its own virulence by inducing expression of the host immune inhibitory ligand CD200.Cell host & microbe · 2011Article
- Nitric oxide short-circuits interleukin-12-mediated tumor regression.Cancer immunology, immunotherapy : CII · 2011Article
- Mouse and human iNKT cell agonist β-mannosylceramide reveals a distinct mechanism of tumor immunity.The Journal of clinical investigation · 2011Article
- Toll-like receptor 4 activation in cancer progression and therapy.Clinical & developmental immunology · 2011Review
- Mature natural killer cells with phenotypic and functional alterations accumulate upon sustained stimulation with IL-15/IL-15Ralpha complexes.Proceedings of the National Academy of Sciences of the United States of America · 2010Article
- The anti-angiogenic activity of IL-12 is increased in iNOS-/- mice and involves NK cells.Journal of molecular medicine (Berlin, Germany) · 2010Article
- Lower levels of gamma interferon expressed by a pseudotyped single-cycle simian immunodeficiency virus enhance immunogenicity in rats.Journal of virology · 2009Article
- Control of parasitophorous vacuole expansion by LYST/Beige restricts the intracellular growth of Leishmania amazonensis.PLoS pathogens · 2008Article
- Exogenous IFN-gamma ex vivo shapes the alloreactive T-cell repertoire by inhibition of Th17 responses and generation of functional Foxp3+ regulatory T cells.European journal of immunology · 2008Article
- Immunosenescence and macrophage functional plasticity: dysregulation of macrophage function by age-associated microenvironmental changes.Immunological reviews · 2005Review
- Immunological properties and vaccine efficacy of murine dendritic cells simultaneously expressing melanoma-associated antigen and interleukin-12.Cancer gene therapy · 2005Article
- Metabolic mechanisms of tumor resistance to T cell effector function.Immunologic research · 2005Review
- Interleukin-12 therapy reduces the number of immune cells and pathology in lungs of mice infected with Mycobacterium tuberculosis.Infection and immunity · 2004Article
- High dose interleukin-12 exacerbates Bordetella pertussis infection and is associated with suppression of cell-mediated immunity in a murine aerosol challenge model.Clinical and experimental immunology · 2004Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Recombinant interleukin 12 (IL-12) can profoundly suppress cellular immune responses in mice. To define the underlying mechanism, recombinant murine (rm)IL-12 was given to C57BL/6 mice undergoing alloimmunization and found to transiently but profoundly suppress in vivo and in vitro allogeneic responses and in vitro splenocyte mitogenic responses. Use of neutralizing antibodies and genetically deficient mice showed that IFN-gamma (but not TNF-alpha) mediated rmIL-12-induced immune suppression. Splenocyte fractionation studies revealed that adherent cells from rmIL-12-treated mice suppressed the mitogenic response of normal nonadherent cells to concanavalin A and IL-2. Addition of an inhibitor of nitric oxide synthase (NOS) restored mitogenic responses, and inducible (i)NOS-/- mice were not immunosuppressed by rmIL-12. These results support the view that suppression of T cell responses is due to NO produced by macrophages responding to the high levels of IFN-gamma induced by rmIL-12. When a NOS inhibitor was given with rmIL-12 during vaccination of A/J mice with irradiated SCK tumor cells, immunosuppression was averted and the extent of rmIL-12's ability to enhance induction of protective antitumor immunity was revealed. This demonstrates that rmIL-12 is an effective vaccine adjuvant whose efficacy may be masked by its transient immunosuppressive effect.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.