PMID- 7830406
OWN - NLM
STAT- MEDLINE
DCOM- 19950217
LR  - 20071115
IS  - 0022-4804 (Print)
IS  - 0022-4804 (Linking)
VI  - 58
IP  - 1
DP  - 1995 Jan
TI  - The effect of soluble tumor necrosis factor receptor-II on endotoxin-mediated 
      hemodynamic instability.
PG  - 53-7
AB  - Tumor necrosis factor-alpha (TNF-alpha), a central mediator in the hemodynamic 
      response to injury and infection, is a primary mediator of endotoxin-induced 
      hemodynamic instability. Two types of naturally occurring soluble TNF receptors 
      circulate in human experimental endotoxemia and the recombinant proteins of both 
      have been hypothesized as potential therapeutic agents antagonizing TNF-mediated 
      effects of endotoxemia. The administration of recombinant sTNFr-I has been 
      previously shown to attenuate the hemodynamic collapse of lethal bacteremia. In 
      the current study, we investigated the role of recombinant sTNFR-II at low (0.5 
      mg/kg) and high (2.5 mg/kg) doses as a potential therapeutic agent for the 
      inhibition of endotoxin lipopolysaccharide (LPS)-mediated hemodynamic 
      instability. Eighteen male Sprague-Dawley rats were anesthetized and cannulated 
      for continuous blood pressure monitoring and cardiac output measurement by 
      thermodilution. Groups of animals received saline, LPS (1 mg/kg), or sTNFr-II (at 
      0.5 or 2.5 mg/kg) 15 min prior to LPS (1 mg/kg). Hemodynamic variables (blood 
      pressure, cardiac output, heart rate) were monitored every 15 min for 2 hr. LPS 
      caused a 30% decrease in mean arterial pressure by 60 min, which began to recover 
      by 120 min. sTNFr-II was unable to prevent LPS-induced hypotension at low or high 
      dose. Serum levels of immunoreactive TNF-alpha, undetectable in control animals, 
      were significantly increased by sTNFr-II compared to LPS alone. Serum from 
      animals treated with high-dose sTNFr-II showed significantly less TNF 
      cytotoxicity than those treated with low-dose sTNFr-II, indicating that high 
      doses of sTNFr-II are required for the inhibition of the bioactivity of 
      TNF.(ABSTRACT TRUNCATED AT 250 WORDS)
FAU - Anderson, J A
AU  - Anderson JA
AD  - Department of Surgery, University of Louisville School of Medicine, Kentucky 
      40292.
FAU - Knott, A W
AU  - Knott AW
FAU - Wilson, M A
AU  - Wilson MA
FAU - Garrison, R N
AU  - Garrison RN
FAU - Sims, D E
AU  - Sims DE
FAU - Edwards, M J
AU  - Edwards MJ
LA  - eng
GR  - CA 57527-01/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Surg Res
JT  - The Journal of surgical research
JID - 0376340
RN  - 0 (Endotoxins)
RN  - 0 (Receptors, Tumor Necrosis Factor)
RN  - 0 (Recombinant Proteins)
SB  - IM
MH  - Animals
MH  - Blood Cell Count/drug effects
MH  - Cardiovascular System/drug effects
MH  - Endotoxins/*pharmacology
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Escherichia coli
MH  - Hemodynamics/*drug effects
MH  - Male
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, Tumor Necrosis Factor/classification/*physiology
MH  - Recombinant Proteins
MH  - Solubility
EDAT- 1995/01/01 00:00
MHDA- 1995/01/01 00:01
CRDT- 1995/01/01 00:00
PHST- 1995/01/01 00:00 [pubmed]
PHST- 1995/01/01 00:01 [medline]
PHST- 1995/01/01 00:00 [entrez]
AID - S0022-4804(85)71009-8 [pii]
AID - 10.1006/jsre.1995.1009 [doi]
PST - ppublish
SO  - J Surg Res. 1995 Jan;58(1):53-7. doi: 10.1006/jsre.1995.1009.