Received May 16, 2007
Revised June 14, 2007
Accepted after revision June 14, 2007

¹ University of Miami

^* To whom correspondence should be addressed. E-mail: licinio{at}miami.edu.

	Abstract

There is bidirectional communication between the brain and the immune system. Overproduction of interleukin-1-beta (IL-1) leads to systemic inflammatory response syndrome (SIRS). The crucial role of IL-1 in inflammation has been highlighted by studies performed in caspase-1 knockout mice (casp1-/-), transgenic mice that lack mature IL-1 and survive lethal doses of lypopolysaccharide (LPS). We have previously shown that IL-1, its receptor IL-1 receptor I (IL-1RI) and casp1 are expressed within the brain. Moreover, we documented that peripherally-injected LPS triggers a specific spatial-temporal pattern of expression of IL-1 mRNA within the brain suggesting that IL-1 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 wildtype and casp1-/- mice that included differential expression several genes such as cytokines, chemokines, NOS2 and COX-2. A key component of the neurommune-endocrine axis that is increased by IL-1 is corticotropin-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 response to antidepressant treatment. As dysregulation of the neruoimmuno-endocrine axis appears part of the fundamental biological mechanisms that underlie psychiatric disorders, our findings might contribute increase the understanding of the molecular pathways that are altered in these diseases.

Key Words: Immune response, Interleukin, Neuroendocrinology

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