PMID- 12124212
OWN - NLM
STAT- MEDLINE
DCOM- 20020815
LR  - 20200930
IS  - 0363-6135 (Print)
IS  - 0363-6135 (Linking)
VI  - 283
IP  - 2
DP  - 2002 Aug
TI  - Neutralization of IL-18 attenuates lipopolysaccharide-induced myocardial 
      dysfunction.
PG  - H650-7
AB  - Tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) have 
      been implicated in cardiac dysfunction during endotoxemia. Because IL-18 is a 
      proinflammatory cytokine known to mediate the production of TNF-alpha and 
      IL-1beta and to induce the expression of intercellular adhesion molecule-1 
      (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1), we hypothesized that 
      neutralization of IL-18 would attenuate lipopolysaccharide (LPS)-induced cardiac 
      dysfunction. Mice (C57BL/6) were injected with LPS (0.5 mg/kg ip) or vehicle 
      (normal saline), and left ventricular developed pressure (LVDP) was determined by 
      the Langendorff technique. LVDP was depressed by 38% at 6 h after LPS. 
      LPS-induced myocardial dysfunction was associated with increased myocardial 
      levels of TNF-alpha and IL-1beta as well as increased expression of 
      ICAM-1/VCAM-1. Pretreatment with neutralizing anti-mouse IL-18 antibody 
      attenuated LPS-induced myocardial dysfunction (by 92%) and was associated with 
      reduced myocardial IL-1beta production (65% reduction) and ICAM-1/VCAM-1 
      expression (50% and 35% reduction, respectively). However, myocardial TNF-alpha 
      levels were not influenced by neutralization of IL-18. In conclusion, 
      neutralization of IL-18 protects against LPS-induced myocardial dysfunction. 
      IL-18 may mediate endotoxemic myocardial dysfunction through induction of and/or 
      synergy with IL-1beta, ICAM-1, and VCAM-1.
FAU - Raeburn, Christopher D
AU  - Raeburn CD
AD  - Department of Surgery, University of Colorado Health Sciences Center, 4200 E. 
      Ninth Avenue, Box C-320, Denver, CO 80262, USA. christopher.raeburn@uchsc.edu
FAU - Dinarello, Charles A
AU  - Dinarello CA
FAU - Zimmerman, Michael A
AU  - Zimmerman MA
FAU - Calkins, Casey M
AU  - Calkins CM
FAU - Pomerantz, Benjamin J
AU  - Pomerantz BJ
FAU - McIntyre, Robert C Jr
AU  - McIntyre RC Jr
FAU - Harken, Alden H
AU  - Harken AH
FAU - Meng, Xianzhong
AU  - Meng X
LA  - eng
GR  - GM 08315/GM/NIGMS NIH HHS/United States
GR  - GM 49222/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Am J Physiol Heart Circ Physiol
JT  - American journal of physiology. Heart and circulatory physiology
JID - 100901228
RN  - 0 (Antibodies)
RN  - 0 (Interleukin-1)
RN  - 0 (Interleukin-18)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (Vascular Cell Adhesion Molecule-1)
RN  - 126547-89-5 (Intercellular Adhesion Molecule-1)
SB  - IM
MH  - Animals
MH  - Antibodies/pharmacology
MH  - Heart/*drug effects/*physiopathology
MH  - Intercellular Adhesion Molecule-1/metabolism
MH  - Interleukin-1/metabolism
MH  - Interleukin-18/immunology/*metabolism
MH  - Lipopolysaccharides/*pharmacology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Myocardium/cytology/metabolism
MH  - Neutrophils/cytology
MH  - Tumor Necrosis Factor-alpha/biosynthesis
MH  - Vascular Cell Adhesion Molecule-1/metabolism
EDAT- 2002/07/19 10:00
MHDA- 2002/08/16 10:01
CRDT- 2002/07/19 10:00
PHST- 2002/07/19 10:00 [pubmed]
PHST- 2002/08/16 10:01 [medline]
PHST- 2002/07/19 10:00 [entrez]
AID - 10.1152/ajpheart.00043.2002 [doi]
PST - ppublish
SO  - Am J Physiol Heart Circ Physiol. 2002 Aug;283(2):H650-7. doi: 
      10.1152/ajpheart.00043.2002.