Yang-Soo Kim, MD1; Jung-Man Kim, MD1; Yun-Gyoung Lee, MS1

Oak-Kee Hong, PhD1; Hyuk-Sang Kwon, MD1; Jong-Hoon Ji, MD2

Abstract
Background:  
The purpose of this study was to investigate the presence of intercellular adhesion molecule-1 (ICAM-1) in shoulders with adhesive capsulitis (“frozen shoulder”).

Methods:  
Glenohumeral capsular tissue was obtained from twenty-six patients (seventeen with adhesive capsulitis and nine controls), and ICAM-1 was evaluated with use of oligonucleotide arrays, real-time reverse transcription-polymerase chain reaction (RT-PCR), and immunohistochemistry. ICAM-1 was also evaluated in synovial fluid with use of western blotting (six patients with adhesive capsulitis and two controls) and in peripheral blood with use of an enzyme-linked immunosorbent assay (ELISA) (thirty-two patients with adhesive capsulitis, twenty with diabetes mellitus, and fourteen controls). The effect of ICAM-1 treatment on gene expression of cytokines related to inflammation and fibrosis was evaluated in cultured normal human synovial cells.

Results:  
The level of ICAM-1 was significantly greater in capsular tissue from the glenohumeral joint of patients with adhesive capsulitis compared with controls as measured by oligonucleotide array analysis (0.12 ± 0.01 compared with 0.09 ± 0.00 arbitrary units) (p = 0.001), real-time RT-PCR (1.70 ± 0.19 compared with 0.67 ± 0.24 arbitrary units) (p < 0.05), and immunohistochemical staining. ICAM-1 was also significantly increased in the synovial fluid of patients with adhesive capsulitis (1.70 ± 0.18 arbitrary units) compared with normal controls (0.48 ± 0.17) (p < 0.05) and in serum of patients with adhesive capsulitis (633.22 ± 59.14 ng/mL) and patients with diabetes mellitus (671.25 ± 27.08 ng/mL) compared with controls (359.86 ± 44.29 ng/mL) (p < 0.05). Gene expression of cytokines related to inflammation and fibrosis in synoviocytes cultured in vitro was greater after three days of treatment with ICAM-1 and with ICAM-1 with glucose compared with untreated cells.

Conclusions:  
ICAM-1 was increased in patients with adhesive capsulitis, similar to the increase that has been reported in patients with diabetes mellitus.

Clinical Relevance:  
ICAM-1 may be a therapeutic target for treating adhesive capsulitis.