Previously, we proposed the hypothesis that similarities in the inflammatory response observed in acne vulgaris and degenerative disc disease (DDD), especially the central role of interleukin (IL)-1β, may be further evidence of the role of the anaerobic bacterium Cutibacterium (previously Propionibacterium) acnes in the underlying aetiology of disc degeneration. To investigate this, we examined the upregulation of IL-1β, and other known IL-1β-induced inflammatory markers and neurotrophic factors, from nucleus-pulposus-derived disc cells infected in vitro with C. acnes for up to 48 h. Upon infection, significant upregulation of IL-1β, alongside IL-6, IL-8, chemokine (C-C motif) ligand 3 (CCL3), chemokine (C-C motif) ligand 4 (CCL4), nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), was observed with cells isolated from the degenerative discs of eight patients versus non-infected controls. Expression levels did, however, depend on gene target, multiplicity and period of infection and, notably, donor response. Pre-treatment of cells with clindamycin prior to infection significantly reduced the production of pro-inflammatory mediators. This study confirms that C. acnes can stimulate the expression of IL-1β and other host molecules previously associated with pathological changes in disc tissue, including neo-innervation. While still controversial, the role of C. acnes in DDD remains biologically credible, and its ability to cause disease likely reflects a combination of factors, particularly individualised response to infection.

Central European Institute of Technology Masaryk University 625 00 Brno Czech Republic

Centre of Experimental Rheumatology Department of Rheumatology University Hospital University of Zurich 8091 Zurich Switzerland

Department of Biology Faculty of Medicine Masaryk University 601 77 Brno Czech Republic

Department of Microbiology Faculty of Medicine St Anne's University Hospital Masaryk University 656 91 Brno Czech Republic

Department of Neurosurgery St Anne's University Hospital Masaryk University 656 91 Brno Czech Republic

Department of Neurosurgery University Hospital Brno Masaryk University 625 00 Brno Czech Republic

Department of Orthopaedic Surgery Physical Medicine and Rehabilitation University of Munich 80331 Munich Germany

Department of Orthopaedic Surgery University Hospital Brno Masaryk University 625 00 Brno Czech Republic

Department of Physical Medicine and Rheumatology Balgrist University Hospital University of Zurich 8091 Zurich Switzerland

Laboratory of Bacterial Pathogenesis and Immunology Rockefeller University 1230 York Avenue New York NY 10065 USA

Nutrition Innovation Centre for Food and Health School of Biomedical Sciences Ulster University Coleraine BT52 1SA UK

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