Abstract
It has been reported that the intraarticular injection of hyaluronan (HA), especially that of a high molecular weight (M. W.), provides symptomatic relief and improves joint function in arthritic joints. However, neither the mode of action nor the mechanism of the therapeutic effects is fully understood.
We tried to clarify the effects of HA injection from the aspect of histological features, using immunohistochemical markers in the synovial tissues of the knee joints of patients with rheumatoid arthritis (RA) before and after the injection of high molecular HA. Thirteen patients who met the American Reumatism Association criteria for RA were examined in this study. 2.5 ml hyaluronan (10 mg/ml) was injected weekly into the knee joint five times, 125 mg totally.
Histological parameters that we compared were as follows : 1) grade of synovial proliferation ; number of synovial cells in superficial layer demonstrated by hematoxylin-eosin staining, 2) grade of vascular proliferation ; density of small vessels represented by UEA-1, a lectins, 3) grade of inflammatory cell infiltration by, a) density of macrophages (KP-1), b) density of T lymphocytes (UCHL 1) and c) grade of B lymphocytes aggregation (L26), 4) a) density of Matrix Metallo-proteinase-3, b) density of Cathepsin D, and 5) degree of hyaluronan density and distribution by hyaluronan binding protein (HABP) .
Five of the 13 patients were responders and 8 were non-responders clinically. The difference in immunohistochemical study between responders and non-responders, was the decrease of inflammatory cell density such as macrophages, T lymphocytes, and B lymphocytes, while the density of MMP-3 and cathepsin D containing cells did not decreased. As a result of the diagnosis of their knees, the 5 responders were all evaluated as being in grade I of Larsen Classification, and the proteinase production in their synovial membrane was comparatively mild. From these results, it seems that injected HA has a mild effect in decreasing the inflammation of the synovia.
