Studies on the Mechanism of the Shwartzman

The intradermal injection of filtered bacterial toxin derived from certain Gram-negative microorganisms produces, in rabbits, little evidence of primary damage to the skin other than varying degrees of local inflammatory reaction. The skin may show mild erythema, usually with slight thickening of the injected area. Mter an interval of 12 to 18 hours, an intravenous injection of the same material causes the appearance of extensive hemorrhagic necrosis in the prepared skin site. This reaction, first described in 1928 (1), has become generally known as the Shwartzman phenomenon. No satisfactory explanation of its pathogenesis has yet been made. Very little is known about the basic mechanisms which are implicated in cellular injury of any sort. In recent years, interest in the general problem of tissue damage has been stimulated by wartime investigations into the traumatic effects of arsenical poisons (2) and nitrogen mustards (3), which have demonstrated that certain types of tissue damage may be correlated with biochemical alterations involving cellular enzyme systems. It is probable that the various types of tissue injury caused by bacteria and their products, or by antigen-antibody reactions, will eventually become explainable at a biochemical level. As an approach to this problem, the Shwartzman phenomenon offers an experimental model in which one variety of injury can be studied from this point of view. The phenomenon is, in a sense, non-specific. Preparation of the skin with culture filtrate from one bacterial species renders the skin susceptible to hemorrhage when filtrate from an entirely unrelated species is injected intravenously. Preparation of the skin can be accomplished by inducing local infection with certain living bacteria;i.e., streptococci, staphylococci, and pneumococci, as well as by local virus infection (vaccinia) (4). The capacity of antigen-antibody combinations to bring about the phenomenon has been studied in detail by Shwartzman (4). He showed that rabbits