{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T15:33:26Z","timestamp":1759937606176,"version":"3.40.5"},"reference-count":30,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2021,4,11]],"date-time":"2021-04-11T00:00:00Z","timestamp":1618099200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Fundamemntal Clinical Pharma"],"published-print":{"date-parts":[[2021,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Methotrexate (MTX) is used as anchor drug for patients with early and established rheumatoid arthritis (RA). Vitamin K<jats:sub>2<\/jats:sub> administration was also reported to be associated with decreased disease activity in RA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objectives<\/jats:title><jats:p>Immunosuppressive pharmacodynamics of vitamin K<jats:sub>2<\/jats:sub> combined with MTX was investigated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Mitogen\u2010activated peripheral blood mononuclear cells (PBMCs) were used to evaluate immunosuppressive pharmacodynamics of drugs in vitro.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Vitamin K<jats:sub>2<\/jats:sub> alone dose\u2010dependently suppressed T cell mitogen\u2010activated proliferation of PBMCs of both healthy subjects and RA patients. 446.5 and 2232.5\u00a0ng\/mL vitamin K<jats:sub>2<\/jats:sub> significantly decreased the IC<jats:sub>50<\/jats:sub> values of MTX on the proliferation of PBMCs of RA patients, with little influences on the pharmacodynamics of MTX in the healthy PBMCs. 4465\u00a0ng\/mL vitamin K<jats:sub>2<\/jats:sub> potentiated the pharmacodynamics of MTX in both RA patients and healthy PBMCs. The additional effects of vitamin K<jats:sub>2<\/jats:sub> to potentiate the suppressive effects of MTX seemed not to be related to the regulation of CD4<jats:sup>+<\/jats:sup>CD25<jats:sup>+<\/jats:sup> T cells or CD4<jats:sup>+<\/jats:sup>CD25<jats:sup>+<\/jats:sup>Foxp3<jats:sup>+<\/jats:sup> Treg cells. MTX alone at 100\u00a0ng\/mL significantly decreased the percentage of CD4<jats:sup>+<\/jats:sup> T cells in PBMCs of healthy subjects (<jats:italic>p<\/jats:italic>\u00a0&lt;\u00a00.001) with a slight influence in that of RA patients (not significant) and the combination did not show synergistic inhibitory effect. Vitamin K<jats:sub>2<\/jats:sub> alone tended to suppress the secretion of IL\u201017, IFN\u2010\u03b3, and TNF\u2010\u03b1 from the activated PBMCs of RA patients with smaller influences on the cytokine productions from healthy PBMCs. These additional effects of vitamin K<jats:sub>2<\/jats:sub> were also observed in combination with MTX.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The above information may partially elucidate the potentiation effects of vitamin K<jats:sub>2<\/jats:sub> on the immunosuppressive efficacy of MTX.<\/jats:p><\/jats:sec>","DOI":"10.1111\/fcp.12676","type":"journal-article","created":{"date-parts":[[2021,3,29]],"date-time":"2021-03-29T12:31:25Z","timestamp":1617021085000},"page":"832-842","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Effects of vitamin K<sub>2<\/sub> combined with methotrexate against mitogen\u2010activated peripheral blood mononuclear cells of healthy subjects and rheumatoid arthritis 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