Hyaluronidase activity in the skin, rheumatic disease, and salicylates.

This study* was undertaken to ascertain the effect of salicylate on the spreading activity of testicular extract (T.E.) in the human skin, and its relationship to rheumatic disease. Introduction Hyaluronidase.-It was shown by Duran-Reynals (1928) and McClean (1930) that testicular extract would enhance the infection by vaccinia virus. DuranReynals (Hoffman and Duran-Reynals, 1930) further noted that the spread of inert particulate matter (india ink) was enhanced by T.E. In these experiments intradermal injections of T.E. and india ink were made into the shaved skin of rabbits. The wheals which resulted from the injection of T.E. disappeared more rapidly than did the controls of saline and india ink, and the area of spread for the former was greater than for the latter, the maximum spread being reached in one hour. Variations in the histological pictures of the two areas was also noted. This explanation of the enhancing of the spread of infection by T.E. is now generally accepted, and the group of substances which show this phenomenon are referred to as the " spreading factors ". The hypothesis of increased permeability of the tissues induced by T.E. was given factual support by Chain and Duthie (1939; 1940). The evidence was put forward that the spreading factors operated by reducing the viscosity of the mucoid ground substance of the connective tissues, and that the spreading factors were, in fact, enzymes. These enzymes reduce the viscosity of hyaluronic acid derived from synovial and ocular fluids, and were therefore termed hyaluronidases. Viscosimetric methods were devised and an accurate assay of the spreading factors could be made under controlled conditions. Hyaluronidase was shown to be thermolabile and susceptible to changes of pH. Testicular extracts have been purified to obtain hyaluronidase in a highly concentrated state. The enzyme can be assayed in vitro by various methods (Chain and Duthie, 1940; Swyer and Emmens, 1947), or biologically in the experimental animal (Madinaveitia, 1938). Hyaluronidases have been extracted from a wide variety of bacteria, including Group A haemolytic streptococci; and in the case of the latter there appears to be some relationship between the production of mucoid capsules, enzymatic activity, and virulence (Meyer, Hobby, and others, 1940).