Pharmacogenomics of neuroimmune interactions in human psychiatric disorders

Julio Licinio, Claudio Mastronardi, Ma Li Wong

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22 Citations (Scopus)


There is bidirectional communication between the brain and the immune system. Overproduction of interleukin-1β (IL-1β) leads to systemic inflammatory response syndrome (SIRS). The crucial role of IL-1β in inflammation has been highlighted by studies performed in caspase-1 knockout mice (casp1-/-), transgenic mice that lack mature IL-1β and survive lethal doses of lypopolysaccharide (LPS). We have previously shown that IL-1β, 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-1β mRNA within the brain, suggesting that IL-1β 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-1β 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.

Original languageEnglish
Pages (from-to)807-811
Number of pages5
JournalExperimental Physiology
Issue number5
Publication statusPublished or Issued - Sep 2007

ASJC Scopus subject areas

  • Physiology
  • Nutrition and Dietetics
  • Physiology (medical)

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