The effects of sparingly soluble corticosteroid suspensions prepared for intraarticular therapy, of their vehicles, and of hydrocortisone on synovial hyaluronic acid (HA) synthesis were compared in organ cultures of normal canine villous synovium. Both hydrocortisone and the corticosteroid suspensions suppressed HA synthesis, as did 2 vehicle components, polysorbate 80 and myristyl-gamma-picrolinium chloride. Cultures of synovium from joints of dogs which, 1 day previously, had been injected with methylprednisolone acetate suspension synthesized less HA than did control cultures from noninjected joints of the same animals. The results indicate that suppression of HA synthesis is a mechanism by which these drugs can act to reduce joint HA content and promote resolution of synovial effusions.Suspensions of microcrystalline corticosteroids, which can be injected into joints or periarticular tissues, have become important clinical tools for the physician. The soluble corticosteroids first used for intraarticular therapy had beneficial, but transient, effects. The subsequent availability of chemically modilhed and relatively insoluble corticosteroids, such as miethylprednisolone acetate, hydrocortisone tebutate, prednisolone tebutate, and triamcinolone The site of action of these drugs appears to be the synovium, but their effects there have not been well defined. Estimates of the relative efficacy and duration of action of the available formulations have been based on clinical experience gained in treating patients with arthritis (2). Customary doses have been derived empirically, with little information available regarding the joint space bioavailability or half-life of the drugs (1).A satisfactory clinical response to intraarticular corticosteroid treatment usually includes a reduction in the volume of synovial fluid. Several observations suggest that this reflects reduced synovial blood flow, which is produced either by a direct corticosteroid effect on synovial blood vessels or by effects on mediators of vascular resistance or permeability, such as prostaglandins or histamine (3,4). The concentration of hyaluronic acid (HA) in synovial effusions is lower than that in normal joint fluid (3, but large effusions indicate an increase in the total HA content of the joint.It was speculated 30 years ago that corticosteroids might decrease HA synthesis by synovial lining cells and thus reduce the amount of HA present in the joint (6). This hypothesis is consistent with the results of experiments in which hydrocortisone (lo-' to 10-7M) inhibited synthesis of HA and sulfated glycosaminoglycans (GAG) in synovial cell cultures (7,8). Other in vitro studies have demonstrated a suppressive effect of hydrocortisone, dexamethasone, or prednisolone on synthesis of DNA, proteoglycans, prostaglandins, collagen, collagenase, proteoglycanase, catabolin, and other proteins (8-12). There
