Increased levels of inflammatory markers in the subscapularis tendon and joint capsule in patients with subacromial impingement

Knee Surg Sports Traumatol Arthrosc. 2021 Jul;29(7):2228-2236. doi: 10.1007/s00167-020-05992-9. Epub 2020 Apr 30.


Purpose: To analyze biopsy samples from the subscapularis tendon and from the joint capsule from male patients with subacromial impingement syndrome and compare them with samples from male patients with post-traumatic recurrent shoulder instability, to detect increased inflammatory activity that might be present inside the humeroscapular joint.

Methods: Twenty male patients scheduled for surgery for either subacromial decompression or Bankart reconstruction were included. Four biopsies from each patient were obtained during surgery from the capsule and the subscapularis tendon. Each specimen was analyzed for TNF-α, IL-6, CD-3 and CD-72. Multiplex fluorescence immunohistochemistry was performed on histological samples from the capsule and tendon to demonstrate the level of inflammatory markers. Fluorescence microscope images were acquired using an automated scanning system. On each slide, the number of pixels was registered and used in the analyses.

Results: The subacromial impingement syndrome group comprised eight patients, median age 53 (45-74) years, while the instability group 12, median age 27 (22-48) years (p < 0.00001). The amount of IL-6 and TNF-α was significantly higher in the subscapularis tendon of the patients with subacromial impingement syndrome compared with instability patients (p = 0.0015 and p = 0.0008 respectively). In the capsular samples, significantly higher amount of TNF-α and CD-72 was found in patients with subacromial impingement syndrome compared with instability patients (p < 0.0001 for both). On the other hand, the amount of CD-3 was significantly higher in the instability group (p = 0.0013).

Conclusions: This study provides evidence that an extended inflammatory process is present, not only in the subacromial bursa but also in the glenohumeral joint in patients with subacromial impingement syndrome.

Level of evidence: Level III.

Clinical relevance: To develop a treatment targeted towards intra-articular inflammatory cytokines appears appealing.

Keywords: Biopsy analyses; Cytokines; Pathogenesis; Shoulder arthroscopy; Shoulder instability; Subacromial impingement syndrome.

MeSH terms

  • Aged
  • Biomarkers / analysis
  • Biopsy / methods
  • Bursa, Synovial / pathology
  • Cytokines / analysis*
  • Decompression, Surgical / methods
  • Humans
  • Inflammation / metabolism
  • Interleukin-6 / analysis
  • Joint Capsule / pathology*
  • Joint Capsule / surgery
  • Joint Instability / blood
  • Joint Instability / surgery
  • Male
  • Middle Aged
  • Plastic Surgery Procedures / methods
  • Rotator Cuff / pathology*
  • Rotator Cuff / surgery
  • Shoulder / surgery
  • Shoulder Impingement Syndrome / pathology*
  • Shoulder Impingement Syndrome / surgery
  • Shoulder Joint / surgery
  • Tendons / pathology*
  • Tendons / surgery
  • Tumor Necrosis Factor-alpha / analysis


  • Biomarkers
  • Cytokines
  • Interleukin-6
  • Tumor Necrosis Factor-alpha