IMMUNOLOCALIZATION OF CYTOKINES AND THEIR RECEPTORS IN ADHESIVE CAPSULITIS OF THE SHOULDER

The purpose of this study was to test the hypothesis that specific cyt okines are involved in the initiation and evolution of the fibrotic pr ocess in adhesive capsulitis of the shoulder. After approval from the Institutional Review Board, biopsies of shoulder capsule and synovium were collected during shoulder arthroscopy from 19 patients with adhes ive capsulitis, 14 patients with nonspecific synovitis and no fibrosis or clinical evidence of adhesive capsulitis, and seven patients under going surgery for another pathology who had a normal capsule and synov ium. Immunohistochemical localization with monoclonal antibodies to tr ansforming growth factor-beta and its receptor, platelet-derived growt h factor and its receptor, basic fibroblast growth factor, interleukin -1 beta, tumor necrosis factor-alpha, and hepatocyte growth factor was performed using standard immunoperoxidase techniques. The frequency o f cytokine staining was correlated with the clinical diagnosis. Synovi al cells, fibroblasts, T-cells, and B-cells were identified with speci fic antibodies, and newly synthesized matrix was examined for type-I a nd type-III collagen by immunohistochemical staining. The predominant cell types present were synovial cells and fibroblasts. Staining for t ype-III collagen in adhesive capsulitis tissues indicated new depositi on of collagen in the capsule. There was staining for transforming gro wth factor-beta and its receptor, platelet-derived growth factor and i ts receptor, interleukin-1 beta, and tumor necrosis factor-alpha in ad hesive capsulitis and nonspecific synovitis tissues, compared with min imal staining in normal capsule. Staining was more frequent in synovia l cells than in capsular cells. The frequency of cell and matrix stain ing for transforming growth factor-beta, platelet-derived growth facto r, and hepatocyte growth factor was greater in adhesive capsulitis tis sues than in those from patients with nonspecific synovitis. No differ ence in the frequency of staining between primary (idiopathic) and sec ondary adhesive capsulitis was found. The results of this study indica te that adhesive capsulitis involves both synovial hyperplasia and cap sular fibrosis. Cytokines such as transforming growth factor-beta and platelet-derived growth factor may be involved in the inflammatory and fibrotic processes in adhesive capsulitis. Matrix-bound transforming growth factor-beta may act as a persistent stimulus, resulting in caps ular fibrosis. Understanding the basic pathophysiology of adhesive cap sulitis is an important step in the development of clinically useful a ntifibrotic agents that may serve as novel treatments for patients wit h this condition.