{
  "abstract": "Infective endocarditis (IE) is characterized by systemic inflammation, yet the contribution of cytokine network dysregulation to clinical outcomes remains poorly understood. We aimed to evaluate cytokine co-expression patterns in IE and identify immune network signatures associated with in-hospital mortality and major complications. We conducted a prospective cohort study of adult patients hospitalized with IE at a quaternary public hospital in Brazil (2012-2024). Serum cytokines and chemokines were measured at one to three time points during hospitalization. Weighted topological overlap (wTO) and Co-expression Differential Network Analysis (CoDiNA) were used to characterize cytokine interactions in baseline. Logistic mixed-effects models assessed associations between individual cytokines and in-hospital mortality. Of 305 screened patients, 160 met inclusion criteria (41 deaths; in-hospital mortality 25.6%). Survivors exhibited dense, integrated cytokine interaction networks, whereas non-survivors showed markedly fragmented networks with loss of connectivity across multiple cytokines. IFN-γ and IL-1RA formed a preserved but isolated axis in fatal cases, while IL-7 displayed outcome-specific connectivity in patients with infectious complications. A distinct triad involving IFN-γ, IL-1RA, and IL-6 differentiated patients with cardiac complications. In multivariable models adjusted for age, sex, and sampling time, CCL2 was independently associated with in-hospital mortality. Immune network disruption is strongly associated with adverse outcomes in IE. Distinct cytokine signatures, including altered interactions of IFN-γ, IL-1RA, IL-6, IL-7, and CCL2, identify high-risk patients and reveal potential biological pathways underlying clinical deterioration.",
  "abstract_shown": true,
  "affiliations": [
    "Programa de Pós-Graduação em Ciências Aplicadas à Saúde do Adulto, Faculdade de Medicina da Universidade Federal de Minas Gerais, Avenida Professor Alfredo Balena, 190, Santa Efigênia, Belo Horizonte 30130-100, MG, Brazil.",
    "Hospital das Clínicas da Universidade Federal de Minas Gerais, Avenida Professor Alfredo Balena, 110, Santa Efigênia, Belo Horizonte 30130-100, MG, Brazil.",
    "Departamento de Clínica Médica, Faculdade de Medicina da Universidade Federal de Minas Gerais, Avenida Professor Alfredo Balena, 190, Santa Efigênia, Belo Horizonte 30130-100, MG, Brazil.",
    "Diagnostic and Monitoring Biomarkers Laboratory of the Fundação Oswaldo Cruz, Instituto René-Rachou, Avenida Augusto de Lima, 1715-Barro Preto, Belo Horizonte 30190-002, MG, Brazil.",
    "Department of Statistics, Universidade Federal do Paraná, R. XV de Novembro, 1299, Centro, Curitiba 81530-015, PR, Brazil."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 12,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Isabela Galizzi Fae",
      "orcid": "0000-0003-2283-1385"
    },
    {
      "affs": [
        0
      ],
      "name": "Pedro Henrique Oliveira Murta Pinto",
      "orcid": "0009-0007-9579-5203"
    },
    {
      "affs": [
        0
      ],
      "name": "Gustavo Brandão Oliveira"
    },
    {
      "affs": [
        1
      ],
      "name": "Roni Arley Silva Duque",
      "orcid": "0009-0000-7569-9141"
    },
    {
      "affs": [
        2
      ],
      "name": "Fernanda Sophya Leite Cambraia"
    },
    {
      "affs": [
        2
      ],
      "name": "Lucas Chaves Diamante"
    },
    {
      "affs": [
        2
      ],
      "name": "Guilherme Lelis Costa",
      "orcid": "0009-0008-2860-3379"
    },
    {
      "affs": [
        3
      ],
      "name": "Andréa Teixeira-Carvalho"
    },
    {
      "affs": [
        4
      ],
      "name": "Deisy Morselli Gysi"
    },
    {
      "affs": [
        4
      ],
      "name": "José Luiz Padilha da Silva",
      "orcid": "0000-0002-3146-0793"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Teresa Cristina Abreu Ferrari",
      "orcid": "0000-0001-9459-2294"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Maria Carmo Pereira Nunes",
      "orcid": "0000-0001-8801-1828"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/0bynf4fsr8081.bib",
  "cited_by": 0,
  "doi": "10.3390/tropicalmed11100265",
  "fulltext_url": "https://europepmc.org/articles/PMC13709421",
  "id": "0bynf4fsr8081",
  "issns": [
    "2414-6366"
  ],
  "landing_url": "https://europepmc.org/article/MED/42931450",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2713|Infective Endocarditis Diagnosis and Management"
    ]
  ],
  "openalex": "W7214171122",
  "pdf_url": "https://europepmc.org/articles/PMC13709421?pdf=render",
  "pmcid": "PMC13709421",
  "pmid": "42931450",
  "published": "2026-09-24",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/0bynf4fsr8081.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:22:01Z",
      "native_id": "MED:42931450",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42931450"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2713|Infective Endocarditis Diagnosis and Management",
      "subfield": "epidemiology-public-health"
    }
  ],
  "title": "Immune Network Dysregulation Predicts Adverse Outcomes in Infective Endocarditis.",
  "title_text": "Immune Network Dysregulation Predicts Adverse Outcomes in Infective Endocarditis.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:22:01Z",
  "url": "https://research.draconitic.com/paper/0bynf4fsr8081",
  "venue": "Tropical medicine and infectious disease",
  "versions": []
}