Journal of Endotoxin Research

 

Advanced Search

Journal Navigation

Journal Home

Subscriptions

Archive

Contact Us

Table of Contents

Sign In to gain access to subscriptions and/or personal tools.
This Article
Right arrow Full Text (PDF)
Right arrow References
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to Saved Citations
Right arrow Download to citation manager
Right arrow Add to My Marked Citations
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by del Fresno, C.
Right arrow Articles by López-Collazo, E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?
Journal of Endotoxin Research, Vol. 13, No. 1, 39-52 (2007)
DOI: 10.1177/0968051907078623
© 2007 SAGE Publications

Inflammatory responses associated with acute coronary syndrome up-regulate IRAK-M and induce endotoxin tolerance in circulating monocytes

Carlos del Fresno

Research Unit, La Paz' Hospital, Madrid, Spain

Llanos Soler-Rangel

Research Unit, La Paz' Hospital, Madrid, Spain

Alessandra Soares-Schanoski

Research Unit, La Paz' Hospital, Madrid, Spain

Vanesa Gómez-Piña

Research Unit, La Paz' Hospital, Madrid, Spain

María Carmen González-León

Research Unit, La Paz' Hospital, Madrid, Spain

Lourdes Gómez-García

Discover Unit, EMPIREO Molecular Diagnostic, Madrid, Spain

Elena Mendoza-Barberá

Research Unit, La Paz' Hospital, Madrid, Spain

Alexandro Rodríguez-Rojas

Research Unit, La Paz' Hospital, Madrid, Spain

Felipe García

Discover Unit, EMPIREO Molecular Diagnostic, Madrid, Spain

Pablo Fuentes-Prior

Cardiovascular Research Center, ICCC-CSIC, Barcelona, Spain

Francisco Arnalich

Research Unit, La Paz' Hospital, Madrid, Spain

Eduardo López-Collazo

Research Unit, La Paz' Hospital, Madrid, Spain, elopezc.hulp{at}salud.madrid.org

Acute coronary syndrome (ACS) groups different cardiac diseases whose development is associated with inflammation. Here we have analyzed the levels of inflammatory cytokines and of members of the TLR/IRAK pathway including IRAK-M in monocytes from ACS patients classified as either UA (unstable angina), STEMI (ST-elevation myocardial infarction) or NSTEMI (non-ST-elevation myocardial infarction). Circulating monocytes from all patients, but not from healthy individuals, showed high levels of pro-inflammatory cytokines, TNF-{alpha} and IL-6, as well as of IRAK-M and IL-10. TLR4 was also up-regulated, but IRAK-1, IRAK-4 and MyD88 levels were similar in patients and controls. Further, we investigated the consequences of cytokines/IRAK-M expression on the innate immune response to endotoxin. Ex vivo responses to LPS were markedly attenuated in patient monocytes compared to controls. Control monocytes cultured for 6 h in supplemented medium (10% serum from ACS patients) expressed IRAK-M, and LPS stimulation failed to induce TNF-{alpha} and IL-6 in these cultures. Pre-incubation of the serum with a blocking anti-TNF-{alpha} antibody reduced this endotoxin tolerance effect, suggesting that TNF-{alpha} controls this phenomenon, at least partially. We show for the first time that inflammatory responses associated with ACS induce an unresponsiveness state to endotoxin challenge in circulating monocytes, which correlates with expression of IRAK-M, TLR4 and IL-10. The magnitude of this response varies according to the clinical condition (UA, STEMI or NSTEMI), and is regulated by TNF-{alpha}.

Key Words: Acute coronary syndrome • IRAK-M • cytokines • endotoxin tolerance • inflammation • monocytes


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?