HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 92/5/807    most recent expphysiol.2007.038471v1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Licinio, J. Articles by Wong, M.-L. Search for Related Content PubMed PubMed Citation Articles by Licinio, J. Articles by Wong, M.-L. Related Collections Symposia Papers

¹ Department of Psychiatry and Behavioural Sciences, University of Miami Miller School of Medicine, Miami, FL 33136, USA

Abstract

There is bidirectional communication between the brain and the immune system. Overproduction of interleukin-1ß (IL-1ß) leads to systemic inflammatory response syndrome (SIRS). The crucial role of IL-1ß in inflammation has been highlighted by studies performed in caspase-1 knockout mice (casp1^–/–), transgenic mice that lack mature IL-1ß and survive lethal doses of lypopolysaccharide (LPS). We have previously shown that IL-1ß, its receptor IL-1 receptor I (IL-1RI) and caspase-1 are expressed within the brain. Moreover, we documented that peripherally injected LPS triggers a specific spatiotemporal pattern of expression of IL-1ß mRNA within the brain, suggesting that IL-1ß could be a major regulator of the central inflammatory cascade. Therefore, we studied brain transcriptional patterns that occur during LPS-induced SIRS in wild-type and casp1^–/– mice. We showed patterns of gene expression in wild-type and casp1^–/– mice that included differential expression of several genes, such as those for cytokines, chemokines, nitric oxide synthase 2 and cyclo-oygenase 2. A key component of the neuroimmune-endocrine axis that is increased by IL-1ß is corticotrophin releasing hormone (CRH). We found increased response to antidepressants in patients homozygous for the GAG haplotype of CRH receptor-1. Our results support the hypotheses that the CRH receptor-1 gene and possibly other genes in stress–inflammatory pathways are involved in the response to antidepressant treatment. Since dysregulation of the neuroimmune–endocrine axis appears to be one of the fundamental biological mechanisms that underlie psychiatric disorders, our findings might contribute to increase the understanding of the molecular pathways that are altered in these diseases.

(Received 16 May 2007; accepted after revision 14 June 2007; first published online 19 July 2007)
Corresponding author J. Licinio: Department of Psychiatry and Behavioral Sciences (D-28), University of Miami Miller School of Medicine, 1695 NW 9th Avenue, Suite 3100, Miami, FL 33136, USA. Email: licinio{at}miami.edu

This article has been cited by other articles:

				V. Rettori Neuroimmune interactions Exp Physiol, September 1, 2007; 92(5): 799 - 800. [Full Text] [PDF]