The Role of Cutibacterium acnes in Intervertebral Disc Inflammation

Abstract

Recently, the role of infection of the intervertebral disc (IVD) with <i>Cutibacterium acnes</i> (<i>C. acnes</i>) as a contributor to disc-related low back pain (LBP) has been discussed. The aim of this study was to investigate whether and how <i>C. acnes</i> contributes to the inflammatory processes during IVD disease. The prevalence of <i>C. acnes</i> infection in human IVD tissue was determined by aerobic and anaerobic culture. Thereafter, primary human IVD cells were infected with a reference and a clinical <i>C. acnes</i> strain and analyzed for pro-inflammatory markers (gene/protein level). In a subsequent experiment, the involvement of the Toll-like receptor (TLR) pathway was investigated by co-treatment with sparstolonin B, a TLR2/4 inhibitor. We detected <i>C. acnes</i> in 10% of IVD biopsies (with either herniation or degeneration). Stimulating IVD cells with both <i>C. acnes</i> strains strongly and significantly upregulated expression of Interleukin (IL)-1β, IL-6, IL-8, and inducible nitric oxide synthase (iNOS). IL-6, cyclooxygenase (COX)-2, and iNOS expression was reduced upon TLR2/4 inhibition in 3 out of 5 donors, whereby responders and non-responders could not be differentiated by their basal TLR2 or TLR4 expression levels. We demonstrate that exposure of IVD cells to <i>C. acnes</i> induces an inflammatory response that may contribute to the development of discogenic LBP by involving TLR2/4 activation, yet only in a subgroup of patients. Whether the same response will be observed in vivo and where lower inoculums are present remains to be proven in future studies.