Observations on the production of pyrogenic substances by rabbit and human leucocytes

1. The mechanism of release of a pyrogen from leucocytes has been studied in cells obtained from sterile rabbit peritoneal exudates and from rabbit blood. Attempts were made to induce human leucocytes-from blood-to release a pyrogen. 2. Rabbit leucocytes, kept below 4 degrees C., were not pyrogenic and did not release any pyrogen when disintegrated. Incubating such cells, in various media, at 37 degrees C. led to the formation of a pyrogen which was heat-labile. The maximum yield was attained after 1(1/2) hours' incubation. 3. The formation of rabbit leucocytic pyrogen was prevented by freezing and thawing the leucocytes, by heating them to 56 degrees C. for half an hour before incubation, and by ageing them in the cold. 4. Nitrofurazone (5-nitro-2-furaldehyde semicarbazone) prevents the formation of leucocytic pyrogen when given by mouth to the cell-donor animals, or when added to leucocytes in intro. 5. Leucocytes from rabbit blood formed leucocytic pyrogen, on incubation in saline, and this formation was also inhibited by nitrofurazone. 6. No leucocytic pyrogen was released from human leucocytes subjected to mechanical, osmotic, or thermal damage, and it was not formed when the cells were incubated in saline. 7. The source of rabbit leucocytic pyrogen, the action of nitrofurazone on leucocytes, and the supposed role of leucocytic pyrogen in fever are discussed.