{
  "abstract": "Chronic inflammation is increasingly recognized as a shared feature across neuropsychiatric, neurodegenerative, metabolic, oncologic, and post-infectious disorders, yet treatments mainly target downstream effects. Evidence suggests dysregulated glucocorticoid receptor (GR; encoded by NR3C1 ) signaling may regulate inflammation upstream, linking stress, HPA axis dysfunction, altered neuroimmune signaling, NF-κB activation, and ongoing inflammation. We review evidence supporting selective modulation of GR as a host-directed therapy targeting this shared mechanism. Across experimental systems, GR modulation is associated with attenuation of NF-κB-associated inflammatory signaling while preserving host-defense and repair-associated pathways. Exploratory clinical observations suggest that biological and therapeutic responses may depend on the degree of GR modulation, providing a hypothesis for prospective evaluation of a potential therapeutic window. Despite remaining questions, convergent evidence views dysregulated GR signaling as a promising upstream target across conditions like post-infectious inflammation, neuropsychiatric disorders, addiction, metabolic disease, and some cancers. We propose a biomarker-guided framework to evaluate selective GR modulation to restore the balance of inflammation in patient groups, rather than just suppressing downstream effects.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Microbiology, Immunology and Pathology, Colorado State University",
    "Neurodegenerative Disease Research Center, Barrow Neurological Institute",
    "Department of Pathology, NYU Grossman School of Medicine, New York University",
    "Baylor College of Medicine",
    "Department of Neuroscience, Medical University of South Carolina",
    "Van Drie Research LLC",
    "Department of Psychology, University of Kentucky",
    "28bio LLC",
    "Pop Test Oncology LLC",
    "Department of Urology, Icahn School of Medicine at Mount Sinai"
  ],
  "article_type": "brief report",
  "arxiv": null,
  "author_total": 13,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Richard A. Slayden"
    },
    {
      "affs": [
        1
      ],
      "name": "Ronald B. Tjalkens"
    },
    {
      "affs": [
        2
      ],
      "name": "Neil D. Theise"
    },
    {
      "affs": [
        3
      ],
      "name": "Christopher D. Verrico"
    },
    {
      "affs": [
        4
      ],
      "name": "Estefania P. Azevedo"
    },
    {
      "affs": [
        5
      ],
      "name": "John H. Van Drie"
    },
    {
      "affs": [
        6
      ],
      "name": "Michael T. Bardo"
    },
    {
      "affs": [
        6
      ],
      "name": "Mark A. Prendergast"
    },
    {
      "affs": [
        7
      ],
      "name": "Christopher M. Butt"
    },
    {
      "affs": [
        8
      ],
      "name": "Randice Altschul"
    },
    {
      "affs": [
        9
      ],
      "name": "Sujit S. Nair"
    },
    {
      "affs": [
        9
      ],
      "name": "Dimple Chakravarty"
    },
    {
      "affs": [
        9
      ],
      "name": "Ashutosh K. Tewari"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/39skq1epsa6pr.bib",
  "cited_by": 0,
  "doi": "10.3389/fphar.2026.1931270",
  "fulltext_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13725057/?tool=EBI",
  "id": "39skq1epsa6pr",
  "issns": [
    "1663-9812"
  ],
  "landing_url": "https://www.frontiersin.org/articles/10.3389/fphar.2026.1931270/full",
  "language": "eng",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Perspective"
    ],
    [
      "openalex",
      "2802|Stress Responses and Cortisol"
    ]
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  "openalex": "W7222916045",
  "pdf_url": "https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2026.1931270/pdf",
  "pmcid": "PMC13725057",
  "pmid": "42973778",
  "published": "2026-10-19",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/39skq1epsa6pr.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:20:06Z",
      "native_id": "10.3389/fphar.2026.1931270",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fphar.2026.1931270/full"
    },
    {
      "first_seen": "2026-11-03T15:20:50Z",
      "native_id": "PMC:PMC13725057",
      "source": "europepmc",
      "url": "https://europepmc.org/article/PMC/PMC13725057"
    },
    {
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      "native_id": "PMC13725057",
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      "url": "https://doi.org/10.3389/fphar.2026.1931270"
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  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:2802|Stress Responses and Cortisol",
      "subfield": "neuroscience"
    }
  ],
  "title": "Glucocorticoid receptor modulation as a host-directed strategy for inflammatory priming across chronic disease states",
  "title_text": "Glucocorticoid receptor modulation as a host-directed strategy for inflammatory priming across chronic disease states",
  "type": "peer-reviewed",
  "updated_at": "2026-11-06T12:21:24Z",
  "url": "https://research.draconitic.com/paper/39skq1epsa6pr",
  "venue": "Frontiers in Pharmacology",
  "versions": []
}