G. Wakabayashi et al., ALTERED INTERLEUKIN-1 AND TUMOR-NECROSIS-FACTOR PRODUCTION AND SECRETION DURING PYROGENIC TOLERANCE TO LPS IN RABBITS, The American journal of physiology, 267(1), 1994, pp. 180000329-180000336
Rabbits were injected intravenously with 10 mu g/kg of endotoxin [lipo
polysaccharide (LPS)] on days 0, 1, and 7, and rectal temperatures wer
e monitored. The febrile responses were compared with circulating leve
ls of interleukin-1 beta (IL-1 beta) and tumor necrosis factor (TNF) a
nd in vitro synthesis of these cytokines by peripheral blood mononucle
ar cells (PBMC) isolated just before the injection of LPS. Fever after
the first LPS injection was biphasic on day 0, attenuated and monopha
sic after the second LPS injection on day 1, and augmented after third
injection of LPS on day 7. On day 1, circulating TNF and IL-1 beta le
vels were significantly (P < 0.05) decreased compared with those on da
ys 0 and 7. Similarly, TNF and IL-1 beta synthesis by LPS-stimulated P
BMC were significantly reduced on day 1. On day 7, cellular synthesis
and secretion of IL-1 beta were significantly increased compared with
that on day 0. A significant positive correlation was observed between
fever index and total in vitro IL-1 beta synthesis by LPS-stimulated
PBMC (r = 0.866, P = 0.001). These data demonstrate that pyrogenic tol
erance in the rabbit after a single LPS injection is associated with d
ecreased circulating IL-1 beta and TNF levels as well as decreased pro
duction of these cytokines in vitro. In addition, the pyrogenic hyperr
esponsiveness to LPS after 7 days is associated with increased synthes
is and secretion of IL-1 beta from PBMC in vitro.