HEMORRHAGES IN TUBERCULOUS GUINEA PIGS AT THE SITE OF INJECTION OF IRRITANTS FOLLOWING INTRAVASCULAR INJECTIONS OF INJURIOUS SUBSTANCES (SHWARTZMAN PHENOMENON)
Authors: Jules Freund
Journal: The Journal of Experimental Medicine (1934)

1. When toxic filtrates from cultures of B coli, B. typhosus, or meningococci are injected into the blood stream, peritoneal cavity, or subcutaneous tissue of tuberculous guinea pigs, the skin at the site of a tuberculin reaction becomes hemorrhagic. The extent of the hemorrhage is proportional to the severity of the tuberculin reaction demonstrable by tests with various dilutions of tuberculin. 2. Tuberculin does not prepare the skin of non-tuberculous guinea pigs for this hemorrhagic reaction. 3. Tuberculin does not produce an intense or necrotic inflammation in the skin of tuberculous rabbits and fails to prepare the skin for the hemorrhagic reaction. 4. Tuberculin injected into the peritoneal cavities of tuberculous guinea pigs causes a hemorrhage in the skin at the site of a tuberculin reaction. 5. All guinea pigs infected with B.C.G., and most of those infected with a virulent strain of tubercle bacilli, when sensitized to horse serum and injected intracutaneously with 0.1 cc. of horse serum, react with redness, edema, and necrosis; and in some instances the necrosis is preceded by hemorrhage. When horse serum is injected into the skin of these guinea pigs in such dilution that only redness and edema result, the subsequent intravascular injection of typhoid filtrate produces hemorrhage at the site of reaction regularly in those infected with B.C.G. and frequently in those infected with a virulent strain. 6. Filtrates from B. coli, B. typhosus, or meningococci injected into the skin of tuberculous guinea pigs do not produce visible inflammation. When these injections are followed by intravascular injections of the same material hemorrhages do not occur in the skin. 7. When concentrated broth or turpentine is introduced into the skin of tuberculous guinea pigs and later typhoid filtrate is injected into the vascular system, hemorrhages do not occur in the skin at the site of inflammation. 8. The majority of guinea pigs that receive an intravascular injection of typhoid filtrate react with hemorrhage at the site of the injection of the silver nitrate. The incidence of hemorrhagic reaction in tuberculous guinea pigs is higher than in non-tuberculous guinea pigs that received similar injections of silver nitrate and typhoid toxin. 9. In tuberculous guinea pigs the skin can be prepared for the hemorrhagic reaction not only by bacterial toxins but also by tuberculin, horse serum, and an inorganic chemical, silver nitrate. 10. In the guinea pig the skin preparatory agents, i.e. tuberculin in the tuberculous guinea pig, diphtheria toxin and silver nitrate in both tuberculous and non-tuberculous guinea pigs, tend to produce hemorrhages in the skin even without subsequent injection of a toxic bacterial product. This property of the skin preparatory agents may be essential in their action. 11. Hemorrhages occur in the skin at the site of tuberculin reaction not only after the intravascular injection of bacterial toxins or tuberculin, but also after the injection of substances of non-bacterial origin; namely, peptone or soluble starch.