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To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.amjmed.2006.03.040 Byline: Judith H. Lichtman (a), Amir Fathi (b), Martha J. Radford (c), Zhenqiu Lin (d), Caroline S. Loeser (e), Harlan M. Krumholz (d)(f)(g)(h) Keywords: Acute myocardial infarction; Mortality; Risk factors Abstract: The study's purpose was to determine the prevalence and prognostic importance of acute, severe, noncardiac conditions present at the time of an acute myocardial infarction (AMI). Author Affiliation: (a) Section of Chronic Disease Epidemiology, Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven, Conn (b) Department of Medicine, Massachusetts General Hospital, Boston, Mass (c) Division of Cardiology, Department of Medicine, New York University Medical Center, New York, NY (d) Center for Outcomes Research and Evaluation, Yale New Haven Hospital, New Haven, Conn (e) Department of Medicine, Yale University School of Medicine, New Haven, Conn (f) Section of Health Policy and Administration, Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven, Conn (g) Section of Cardiovascular Medicine, Department of Medicine, Yale University School of Medicine, New Haven, Conn (h) Robert Wood Johnson Clinical Scholars Program, Yale University School of Medicine, New Haven, Conn. Article History: Revised 20 March 2006 Article Note: (footnote) Dr. Lichtman is supported by grant number 1 K01 DP000085-01 from the Centers for Disease Control and Prevention (CDC). The contents of this article are solely the responsibility of the authors and do not necessarily represent the official views of CDC.

During septic shock, circulating levels of antiinflammatory mediators are increased relative to those of proinflammatory. The reduced capacity of septic shock blood leukocytes in expressing proinflammatory genes in response to bacterial lipopolysaccharide endotoxin LPS may contribute to reductions in these mediators, but the reasons for persistent increases in circulating antiinflammatory mediators are unknown. We determined whether septic shock leukocytes that have adapted to LPS induction of the IL1 gene could continue to express sIL1RA in response to LPS. Septic shock wholeblood leukocytes and neutrophils PMNs selectively maintained production of sIL1RA after treatment with LPS while limiting that of IL1. Repressed transcription of IL1 and rapid decay of IL1 mRNA in septic shock neutrophils correlated with reductions in levels of IL1 after stimulation with LPS. Transcription of sIL1RA mRNA was also suppressed, but the ability of LPS to stimulate events that lead to efficient translation of a stable sIL1RA mRNA appeared responsible for maintaining sIL1RA production. We conclude that LPS adaptation of septic shock leukocytes selectively influences signaling pathways that regulate transcription, mRNA processing, and translation, leading to changes in the balance of production of pro and antiinflammatory mediators.