Inhibitors of Hyaluronidase

Abstract

AN unsolved problem in the study of rheumatic diseases is whether or not hyaluronidase plays any part in the typical changes in the connective tissue, particularly of the interfibrillar cement substance, which is believed to contain hyaluronic acid. Guerra¹, for example, claimed that sodium salicylate significantly inhibits the spreading power of hyaluronidase injected into the skin, and therefore ascribed the value of salicylate in rheumatic fever to an action of the drug on the hyaluronidase–hyaluronic acid system of the body. Meyer² and Dorfman et al.³ confirmed these observations, but gave no experimental data. Later, Meyer and Ragan⁴ argued that the effect claimed by Guerra was due not to the salicylate but to gentisate, a supposed metabolic product of salicylate. Further research has since shown that therapeutic concentrations of salicylate^5,6 or gentisate⁷ are too weak to inhibit hyaluronidase in vitro. Moreover, Swyer⁶, Dalgaard-Mikkelsen⁸ and Jones⁹ failed to find any demonstrable effect of salicylate on the spreading activity of hyaluronidase injected into the rabbit's skin. The evidence is thus contradictory and too weak to ascribe the value of salicylate in rheumatic fever to an inhibition of hyaluronidase.