On the relation of inflammation to the chemical constitution of injurious agents. On the pharmacology of inflammation.

Changes characteristic of an inflammatory reaction caused by the injection of an injurious agent into the peritoneal cavity were measurable by the quantity of peritoneal fluid, by the number of leucocytes that entered the cavity, and by the abundance of exuded protein. Inflammation increased in severity along with ion dissociation and increase of the valence of electrolytes. With chlorides, sulfates, and nitrates it increased in each instance with the valence of their basic ions. The reactions caused by sodium chloride, sodium sulfate, and sodium citrate increased with the valence of their acid ions. Salts of heavy metals which fix and precipitate proteins caused more active inflammation than did other electrolytes. Histamine and arginine caused active inflammatory reactions with similar characteristics. The amino compounds, urea, citrulline, and creatinine, glycine, alanine, histidine, arginine, and histamine, produced inflammatory reaction in the order of severity with which, in foregoing experiments, they had caused necrosis when injected into the dermis. The acids and alkalis that were tested caused active inflammation when their acidity approached pH 1 or their alkalinity pH 11 respectively, but with approximate neutrality the inflammatory reaction became scant. These changes were in accord with the extent of necrosis when acid or alkalis, in foregoing experiments, were injected into the dermis. When histamine or arginine combines with hydrochloric acid to form histamine dihydrochloride or arginine monohydrochloride alkalinity is lost and inflammatory reactions caused by the hydrochlorides are relatively mild. The characteristic changes which accompany histamine and arginine do not occur. The combination of histamine with phosphoric acid to form histamine acid phosphate has similar relation to histamine. Inflammatory reactions caused by monobasic, dibasic, and tribasic sodium phosphate increased in activity in accord with increasing alkalinity referable to the basic ions of these salts. The activity of inflammatory reactions has been found to vary in accord with the chemical constitution of the injurious agents that have been tested.