Proinflammatory cytokines and metalloproteases are expressed in the subacromial bursa in patients with rotator cuff disease

Arthroscopy. 2005 Sep;21(9):1076.e1-1076.e9. doi: 10.1016/j.arthro.2005.05.017.


Purpose: The pathophysiology of subacromial impingement syndrome is poorly understood. We investigated the expression of inflammatory cytokines, metalloproteases, and the cyclooxygenases in the subacromial bursa in control patients and in patients with rotator cuff tear.

Type of study: Basic science evaluation.

Methods: Eighteen patients undergoing shoulder surgery had a subacromial bursa biopsy examination. Patients were divided into 2 groups. Group I (study group) had 10 patients with a full-thickness rotator cuff tear (RCT). Group II (control group) had 8 patients. Seven of 8 underwent shoulder arthroscopy with anterior capsular reconstruction for instability; 1 of 8 underwent open reduction internal fixation for acute proximal humerus fracture. None of the patients in group II had any history of symptoms or signs consistent with subacromial impingement. H&E and immunohistochemical antibody (MMP-1, MMP-9, IL-1, IL-6, TNF-alpha, COX-1, and COX-2) stained specimens were examined by 2 blinded observers using a histologic scale (grade 0 = no staining to grade 4 = intense staining).

Results: Histologic evidence of inflammation was present in all patients with RCT (group I). No or mild inflammation was noted in group II. The average staining grade for inflammatory cytokines (IL-1, IL-6, TNF-alpha) and proteinases (MMP-1 and MMP-9) was significantly more pronounced in the RCT group (P < .001). Cyclooxygenase enzymes (COX-1 and COX-2) were also increased in group II (P < .001).

Conclusions: A high level of expression of inflammatory cytokines, proteinases, and cyclooxygenase enzymes, known to produce a catabolic environment, is present in the subacromial bursa of patients with rotator cuff tear.

Clinical relevance: These findings support the role of nonsteroidal anti-inflammatory drugs and corticosteroids in RCT treatment, and emphasize the importance of subacromial bursectomy to reduce inflammation in RCT surgery.

Publication types

  • Comparative Study

MeSH terms

  • Adrenal Cortex Hormones / therapeutic use
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
  • Biomarkers
  • Biopsy
  • Bursa, Synovial / chemistry*
  • Bursa, Synovial / enzymology
  • Bursa, Synovial / pathology
  • Bursa, Synovial / surgery
  • Bursitis / drug therapy
  • Bursitis / etiology
  • Bursitis / metabolism*
  • Bursitis / pathology
  • Bursitis / surgery
  • Combined Modality Therapy
  • Cyclooxygenase 1 / analysis
  • Cyclooxygenase 2 / analysis
  • Cytokines / analysis*
  • Fracture Fixation, Internal
  • Humans
  • Immunoenzyme Techniques
  • Interleukin-1 / analysis
  • Interleukin-6 / analysis
  • Joint Instability / metabolism
  • Joint Instability / pathology
  • Matrix Metalloproteinase 1 / analysis
  • Matrix Metalloproteinase 9 / analysis
  • Membrane Proteins / analysis
  • Metalloproteases / analysis*
  • Observer Variation
  • Prostaglandin-Endoperoxide Synthases / analysis*
  • Retrospective Studies
  • Rotator Cuff Injuries*
  • Shoulder Fractures / surgery*
  • Shoulder Impingement Syndrome / surgery*
  • Single-Blind Method
  • Staining and Labeling
  • Tumor Necrosis Factor-alpha / analysis


  • Adrenal Cortex Hormones
  • Anti-Inflammatory Agents, Non-Steroidal
  • Biomarkers
  • Cytokines
  • Interleukin-1
  • Interleukin-6
  • Membrane Proteins
  • Tumor Necrosis Factor-alpha
  • Cyclooxygenase 1
  • Cyclooxygenase 2
  • PTGS1 protein, human
  • PTGS2 protein, human
  • Prostaglandin-Endoperoxide Synthases
  • Metalloproteases
  • Matrix Metalloproteinase 9
  • Matrix Metalloproteinase 1