Human monocytes and neutrophils were separated from buffy coats of blood obtained from normal donors. Following incubation with heat-killed staphylococci, monocyte preparations contained 20 times more pyrogenic activity in the supernatant media than did supernates from an equal number of neutrophils. During purification of these
pyrogens it was discovered that these cell preparations each produced a distinct and different
pyrogen. The
pyrogen obtained from neutrophils had a mol wt of 15,000 following
Sephadex G-75 gel filtration, an isoelectric point of 6.9, and could be precipitated and recovered from 50%
ethanol at -10 degrees C. In contrast, the
pyrogen derived from monocyte preparations had a mol wt of 38,000, an isoelectric point of 5.1, and was destroyed in cold
ethanol. Both molecules were unaffected by viral
neuraminidase but biologically destroyed at 80 degrees C for 20 min and with
trypsin at pH 8.0. The febrile peak produced by partially purified neutrophil
pyrogen occurred at 40 min while that from monocytes was at 60 min. In addition, monocyte
pyrogen produced more sustained
fevers for the same peak elevation as neutrophil
pyrogen. These studies demonstrate for the first time two chemically and biologically distinctive
pyrogens derived from circulating human white blood cells and have important implications for our understanding of the pathogenesis of
fever in man.