Abstract
There is bidirectional communication between the brain and the immune system. Overproduction of interleukin-1beta (IL-1beta) leads to systemic inflammatory response syndrome (SIRS). The crucial role of IL-1beta in inflammation has been highlighted by studies performed in caspase-1 knockout mice (casp1(-/-)), transgenic mice that lack mature IL-1beta and survive lethal doses of lypopolysaccharide (LPS). We have previously shown that IL-1beta, 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-1beta mRNA within the brain, suggesting that IL-1beta 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-1beta 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.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.