Smokeless tobacco extract decreases IL-12 production from LPS-stimulated but increases IL-12 from IFN-γ-stimulated macrophages
Modulation of IFN-γ production from T cells by smokeless tobacco extract (STE) could be a factor in periodontal disease. The major inducer of IFN-γ from T cells is bioactive IL-12 (p70), a heterodimeric protein composed of p35 and p40 subunits, while homodimeric IL-12 p40 antagonizes bioactive IL-12. Both p70 and p40 are produced by macrophages in response to lipopolysaccharide (LPS), IFN-γ and/or CD40 ligation. To determine the impact of STE on IL-12 p40, p70 and IFN-γ, splenic T cells were stimulated with anti-CD3 while splenic macrophages were stimulated with LPS in the presence or absence of STE. Production of IL-12 p40 and p70 from LPS-stimulated splenic macrophages and IL-12 p40, p70 and IFN-γ from LPS/anti-CD3-stimulated T cells and macrophages was decreased by STE. To determine the impact of STE on macrophage IL-12 production alone, splenic or peritoneal macrophages were enriched and then stimulated. STE significantly diminished production of IL-12 p40 and p70 from LPS-stimulated peritoneal macrophages, LPS/IFN-γ-stimulated peritoneal and splenic macrophages, but increased production of IL-12 p40 and p70 from IFN-γ/CD40-stimulated splenic macrophages or IFN-γ-stimulated peritoneal macrophages. None of the effects of STE on IL-12 was due to nicotine, rutin or chlorogenic acid. In contrast to STE, nicotine at 100 μg/ml significantly elevated production of IL-12 p40 and p70 from splenic macrophages stimulate by IFN-γ/LPS. The results indicate that STE has a significant overall effect upon IL-12 production. It suppresses p40 and p70 production during responses to LPS or LPS/IFN-γ but augments p40 and p70 production during responses to IFN-γ without LPS. This affect could have a major impact on diseases associated with excessive production of IL-12. © 2002 Elsevier Science B.V. All rights reserved.
Petro, T., Anderson, L., Gowler, J., & Liu, X. (2002). Smokeless tobacco extract decreases IL-12 production from LPS-stimulated but increases IL-12 from IFN-γ-stimulated macrophages. International Immunopharmacology, 2 (2-3), 345-355. https://doi.org/10.1016/S1567-5769(01)00160-6