PMID- 1533231
OWN - NLM
STAT- MEDLINE
DCOM- 19920526
LR  - 20181113
IS  - 0021-9738 (Print)
IS  - 0021-9738 (Linking)
VI  - 89
IP  - 5
DP  - 1992 May
TI  - Interleukin-1 receptor blockade improves survival and hemodynamic performance in 
      Escherichia coli septic shock, but fails to alter host responses to sublethal 
      endotoxemia.
PG  - 1551-7
AB  - The present study was undertaken to evaluate the extent to which an endogenous 
      interleukin-1 (IL-1) response contributes to the hemodynamic and metabolic 
      consequences of sublethal endotoxemia or lethal Gram-negative septic shock. 
      Young, healthy baboons received either a sublethal dose of lipopolysaccharide 
      (LPS) or an LD100 of live Escherichia coli bacteria, and one half of the animals 
      in each group were continuously infused with IL-1 receptor antagonist (IL-1ra). 
      Plasma IL-1 beta was not detected in this model of endotoxemia. Administration of 
      IL-1ra had only minimal effects on the modest hemodynamic and metabolic responses 
      to sublethal endotoxemia, and did not attenuate the plasma cytokine response. In 
      contrast, high circulating levels of IL-1 beta (range 300-800 pg/ml) were seen 
      during lethal E. coli septic shock. IL-1ra treatment significantly attenuated the 
      decrease in mean arterial blood pressure (MAP) (from -72 +/- 8 to -43 +/- 6 mm 
      Hg; P less than 0.05) and cardiac output (from -0.81 +/- 0.17 to -0.48 +/- 0.15 
      liter/min; P less than 0.05), and significantly improved survival from 43 to 100% 
      at 24 h (P less than 0.05). The plasma IL-1 beta and IL-6 responses to lethal E. 
      coli septic shock were also significantly diminished by IL-1ra treatment (P less 
      than 0.05), whereas tumor necrosis factor-alpha (TNF alpha) concentrations were 
      unaffected. We conclude that an exaggerated systemic IL-1 beta response is 
      characteristic of lethal E. coli septic shock, and contributes significantly to 
      the hemodynamic and metabolic consequences of E. coli septic shock. IL-1ra can 
      significantly attenuate the cytokine cascade and improve survival.
FAU - Fischer, E
AU  - Fischer E
AD  - Department of Surgery, Cornell University Medical College, New York 10021.
FAU - Marano, M A
AU  - Marano MA
FAU - Van Zee, K J
AU  - Van Zee KJ
FAU - Rock, C S
AU  - Rock CS
FAU - Hawes, A S
AU  - Hawes AS
FAU - Thompson, W A
AU  - Thompson WA
FAU - DeForge, L
AU  - DeForge L
FAU - Kenney, J S
AU  - Kenney JS
FAU - Remick, D G
AU  - Remick DG
FAU - Bloedow, D C
AU  - Bloedow DC
AU  - et al.
LA  - eng
GR  - CA-52108/CA/NCI NIH HHS/United States
GR  - GM-34695/GM/NIGMS NIH HHS/United States
GR  - GM-40586/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Clin Invest
JT  - The Journal of clinical investigation
JID - 7802877
RN  - 0 (Endotoxins)
RN  - 0 (Interleukin 1 Receptor Antagonist Protein)
RN  - 0 (Interleukin-1)
RN  - 0 (Interleukin-6)
RN  - 0 (Interleukin-8)
RN  - 0 (Proteins)
RN  - 0 (Receptors, Immunologic)
RN  - 0 (Receptors, Interleukin-1)
RN  - 0 (Sialoglycoproteins)
RN  - 0 (Tumor Necrosis Factor-alpha)
SB  - IM
MH  - Animals
MH  - Endotoxins/blood
MH  - Escherichia coli
MH  - Hemodynamics/*drug effects
MH  - Interleukin 1 Receptor Antagonist Protein
MH  - Interleukin-1/metabolism
MH  - Interleukin-6/metabolism
MH  - Interleukin-8/metabolism
MH  - Papio
MH  - Proteins/*pharmacology
MH  - Receptors, Immunologic/*antagonists & inhibitors
MH  - Receptors, Interleukin-1
MH  - Shock, Septic/*physiopathology
MH  - *Sialoglycoproteins
MH  - Tumor Necrosis Factor-alpha/metabolism
PMC - PMC443028
EDAT- 1992/05/01 00:00
MHDA- 1992/05/01 00:01
PMCR- 1992/05/01
CRDT- 1992/05/01 00:00
PHST- 1992/05/01 00:00 [pubmed]
PHST- 1992/05/01 00:01 [medline]
PHST- 1992/05/01 00:00 [entrez]
PHST- 1992/05/01 00:00 [pmc-release]
AID - 10.1172/JCI115748 [doi]
PST - ppublish
SO  - J Clin Invest. 1992 May;89(5):1551-7. doi: 10.1172/JCI115748.