Faculty Collaboration Database

Neutralization of IL-18 attenuates lipopolysaccharide-induced myocardial dysfunction. Am J Physiol Heart Circ Physiol 2002 Aug;283(2):H650-7

Date

07/19/2002

Pubmed ID

12124212

DOI

10.1152/ajpheart.00043.2002

Scopus ID

2-s2.0-0036073147 (requires institutional sign-in at Scopus site)   73 Citations

Abstract

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.

Author List

Raeburn CD, Dinarello CA, Zimmerman MA, Calkins CM, Pomerantz BJ, McIntyre RC Jr, Harken AH, Meng X

Author

Casey Matthew Calkins MD Professor in the Surgery department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Antibodies
Heart
Intercellular Adhesion Molecule-1
Interleukin-1
Interleukin-18
Lipopolysaccharides
Male
Mice
Mice, Inbred C57BL
Myocardium
Neutrophils
Tumor Necrosis Factor-alpha
Vascular Cell Adhesion Molecule-1