TY - JOUR
T1 - Effects of in vivo 'priming' on endotoxin-induced hypotension and tissue injury
T2 - The role of PAF and tumor necrosis factor
AU - Sun, X.
AU - Hsueh, W.
AU - Torre-Amione, G.
PY - 1990
Y1 - 1990
N2 - Exogenously administered tumor necrosis factor-α (TNF) and bacterial endotoxin (LPS) induce shock and tissue injury. Here, the authors studied the effect of endogenous TNF on LPS-induced hypotension and tissue injury and investigated the role of PAF in these responses. Rats were primed with intraperitoneal injection of zymosan 24 hours before, or Bacillus Calmette-Guerin (BCG) 12 to 15 days before intravenous injection of low dose (0.5 mg/kg) LPS. It was found that nonprimed animals showed mild hypotension and moderate leukopenia in response to LPS. In contrast, zymosan-primed rats developed shock and marked leukopenia, and more severe bowel injury than nonprimed rats. The authors then showed that, following LPS injection, zymosan-primed animals had higher TNP and platelet-activating factor (PAF) levels than nonprimed rats. Pretreatment of the animal with PAF antagonist, SRI 63-441, markedly ameliorated the hypotension and tissue injury. Interestingly, BCG-primed rats did not show aggravation of LPS-induced hypotension. Only TNF (but not PAF) level in these animals was increased. Thus, it appears that TNF release alone, without a sufficient increase in PAF, is incapable of causing severe hypotension. However, most of the BCG-primed animals showed tissue injury, which could be prevented by pretreatment with PAF antagonist. The authors discuss the possible mechanisms of this discrepancy between systemic and local responses in BCG-primed animals.
AB - Exogenously administered tumor necrosis factor-α (TNF) and bacterial endotoxin (LPS) induce shock and tissue injury. Here, the authors studied the effect of endogenous TNF on LPS-induced hypotension and tissue injury and investigated the role of PAF in these responses. Rats were primed with intraperitoneal injection of zymosan 24 hours before, or Bacillus Calmette-Guerin (BCG) 12 to 15 days before intravenous injection of low dose (0.5 mg/kg) LPS. It was found that nonprimed animals showed mild hypotension and moderate leukopenia in response to LPS. In contrast, zymosan-primed rats developed shock and marked leukopenia, and more severe bowel injury than nonprimed rats. The authors then showed that, following LPS injection, zymosan-primed animals had higher TNP and platelet-activating factor (PAF) levels than nonprimed rats. Pretreatment of the animal with PAF antagonist, SRI 63-441, markedly ameliorated the hypotension and tissue injury. Interestingly, BCG-primed rats did not show aggravation of LPS-induced hypotension. Only TNF (but not PAF) level in these animals was increased. Thus, it appears that TNF release alone, without a sufficient increase in PAF, is incapable of causing severe hypotension. However, most of the BCG-primed animals showed tissue injury, which could be prevented by pretreatment with PAF antagonist. The authors discuss the possible mechanisms of this discrepancy between systemic and local responses in BCG-primed animals.
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M3 - Article
C2 - 2327475
AN - SCOPUS:0025317754
VL - 136
SP - 949
EP - 956
JO - American Journal of Pathology
JF - American Journal of Pathology
SN - 0002-9440
IS - 4
ER -