The Journal of Experimental Medicine
Avanti Polar Lipids, Inc.
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
Published 15 September 2003. doi:10.1084/jem.20021067
This Article
Right arrow Full Text
Right arrow Full Text (PDF, 134K)
Right arrow PPT slides of all figures
Right arrow Alert me when this article is cited
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new content in the JEM
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Villa, P.
Right arrow Articles by Ghezzi, P.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Villa, P.
Right arrow Articles by Ghezzi, P.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Facebook   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?
© Rockefeller University Press, 0022-1007/2003/9/971 $5.00
The Journal of Experimental Medicine, Volume 198, Number 6, 971-975

Brief Definitive Report

Erythropoietin Selectively Attenuates Cytokine Production and Inflammation in Cerebral Ischemia by Targeting Neuronal Apoptosis

Pia Villa1,2, Paolo Bigini1, Tiziana Mennini1, Davide Agnello1, Teresa Laragione1, Alfredo Cagnotto1, Barbara Viviani3, Marina Marinovich3, Anthony Cerami4, Thomas R. Coleman4, Michael Brines4 and Pietro Ghezzi1,4

1 Mario Negri Institute for Pharmacological Research, 20157 Milan, Italy
2 Consiglio Nazionale delle Ricerche, Institute of Neuroscience, Cellular and Molecular Pharmacology Section, 20129 Milan, Italy
3 Department of Pharmacological Sciences, University of Milan, 20122 Milan, Italy
4 The Kenneth S. Warren Institute, Kitchawan, NY 10562

Address correspondence to Anthony Cerami, The Kenneth S. Warren Institute, 712 Kitchawan Road, Kitchawan, NY 10562. Phone: (914) 762-7668; Fax: (914) 762-7445; email: acerami{at}kswi.org

Ischemic brain injury resulting from stroke arises from primary neuronal losses and by inflammatory responses. Previous studies suggest that erythropoietin (EPO) attenuates both processes. Although EPO is clearly antiapoptotic for neurons after experimental stroke, it is unknown whether EPO also directly modulates EPO receptor (EPO-R)–expressing glia, microglia, and other inflammatory cells. In these experiments, we show that recombinant human EPO (rhEPO; 5,000 U/kg body weight, i.p.) markedly reduces astrocyte activation and the recruitment of leukocytes and microglia into an infarction produced by middle cerebral artery occlusion in rats. In addition, ischemia-induced production of the proinflammatory cytokines tumor necrosis factor, interleukin 6, and monocyte chemoattractant protein 1 concentration is reduced by >50% after rhEPO administration. Similar results were also observed in mixed neuronal-glial cocultures exposed to the neuronal-selective toxin trimethyl tin. In contrast, rhEPO did not inhibit cytokine production by astrocyte cultures exposed to neuronal homogenates or modulate the response of human peripheral blood mononuclear cells, rat glial cells, or the brain to lipopolysaccharide. These findings suggest that rhEPO attenuates ischemia-induced inflammation by reducing neuronal death rather than by direct effects upon EPO-R–expressing inflammatory cells.

Key Words: stroke • erythropoietin • inflammation • apoptosis • ischemia


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


This article has been cited by other articles:



  Home | Help | Feedback | Subscriptions | Archive | Search
TABLE OF CONTENTS