{
  "abstract": "Intervertebral disc degeneration (IVDD) is accompanied by extracellular-matrix disruption, metabolic stress and immune-cell infiltration, but how metabolites mediate communication between disc cells and macrophages remains incompletely defined. This narrative review examines lactate, succinate and kynurenine as candidate signalling metabolites at the macrophage-disc cell interface and proposes an integrative metabolite-centred framework. Evidence is strongest for lactate, which is supported by IVDD-specific studies linking glycolytic adaptation and impaired clearance to acidosis, MCT-dependent metabolic coupling, ASIC/NLRP3 activation, lactylation, cellular senescence and matrix catabolism. Evidence for succinate is more limited: IVDD-specific studies support SIRT5-AIFM1-dependent succinylation and mitochondrial dysfunction, whereas succinate accumulation and SUCNR1-mediated macrophage signalling in human degenerative discs remain unverified. The kynurenine-AhR axis is primarily hypothesis-generating; emerging IVDD-related observations implicate AhR and tryptophan-pathway changes, but a causal kynurenine-AhR macrophage-disc pathway has not been established. We propose that degenerating disc cells may reprogramme the local metabolic microenvironment, thereby altering macrophage functional states and creating a self-amplifying immunometabolic loop that feeds back on disc-cell injury and extracellular-matrix degradation. Future studies should combine spatial immunometabolomics in human tissue with cell-specific and causal intervention experiments to distinguish established mechanisms from context-dependent or extrapolated pathways and to evaluate potential microenvironment-directed therapeutic targets.",
  "abstract_shown": true,
  "affiliations": [
    "Clinical College of Traditional Chinese Medicine, Gansu University of Chinese Medicine, Lanzhou, Gansu, People's Republic of China."
  ],
  "article_type": "review article",
  "arxiv": null,
  "author_total": 9,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Dong Ma",
      "orcid": "0009-0001-1750-1501"
    },
    {
      "affs": [
        0
      ],
      "name": "Jirong Zhao"
    },
    {
      "affs": [
        0
      ],
      "name": "Kaijie Guo"
    },
    {
      "affs": [
        0
      ],
      "name": "Wulong Liu"
    },
    {
      "affs": [
        0
      ],
      "name": "Hongnian Yin"
    },
    {
      "affs": [
        0
      ],
      "name": "Yang Zhan"
    },
    {
      "affs": [
        0
      ],
      "name": "Rui Zhao"
    },
    {
      "affs": [
        0
      ],
      "name": "Jing Wang"
    },
    {
      "affs": [
        0
      ],
      "name": "Tong Ma"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/ce71v1qcee2j3.bib",
  "cited_by": 0,
  "doi": "10.2147/jir.s651180",
  "fulltext_url": "https://europepmc.org/articles/PMC13744178",
  "id": "ce71v1qcee2j3",
  "issns": [
    "1178-7031"
  ],
  "landing_url": "https://europepmc.org/article/MED/42999835",
  "language": "eng",
  "licence": "CC-BY-NC",
  "licence_label": "CC BY-NC",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2732|Spine and Intervertebral Disc Pathology"
    ]
  ],
  "openalex": "W7225111029",
  "pdf_url": "https://europepmc.org/articles/PMC13744178?pdf=render",
  "pmcid": "PMC13744178",
  "pmid": "42999835",
  "published": "2026-11-03",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/ce71v1qcee2j3.ris",
  "sources": [
    {
      "first_seen": "2026-11-09T15:20:34Z",
      "native_id": "MED:42999835",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42999835"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2732|Spine and Intervertebral Disc Pathology",
      "subfield": "surgery"
    }
  ],
  "title": "Metabolite-Driven Immunometabolic Crosstalk in Intervertebral Disc Degeneration: The Macrophage-Disc Cell Interface.",
  "title_text": "Metabolite-Driven Immunometabolic Crosstalk in Intervertebral Disc Degeneration: The Macrophage-Disc Cell Interface.",
  "type": "peer-reviewed",
  "updated_at": "2026-11-09T15:20:34Z",
  "url": "https://research.draconitic.com/paper/ce71v1qcee2j3",
  "venue": "Journal of inflammation research",
  "versions": []
}