Abstract
Recently the presence of the crosstalks among neuro- and immune systems involved in maintaining the homeostasis has been established. Cytokines and catecholamines may constitute a significant portion of the regulatory networks. It has been reported that IκB expression is regulated by norepinephrine (NE) at both transcriprional and post-transcriptional levels, which could contribute to the observed anti-inflammatory properties of NE. We examined the alteration of inflammatory cytokine expression levels and NE content at locus coeruleus (LC) after peripheral lipopolysaccharide (LPS) injection.The mRNA expression levels of genes encoding IκBα, IL-1β, TNF-α within the LC of C3H/HeN mice (male, 8W) were measured after 5 μg of LPS injection. The IκBα mRNA expression level increased within 1 hr and reached a maximum level at 2 hr. The mRNA expression levels of IL-1β, TNF-α increased within 2 hr, reached a maximum level at 4 hr, and increased at 15-24 hr again. By contrast, NE content at LC decreased at 24 hr. Pretreatment of animals with CP-154, a corticotropin releasing factor type 1 receptor antagonist, did not affect the increase in mRNA expression caused by LPS injection. Collectively, the quick up-regulation of inflammatory cytokine mRNA expression at LC after peripheral LPS injection may be caused by the activation of neural circuit, not by humoral factors transmitted into brain. The research is currently in progress in order to elucidate the relationship between the change of NE content and inflammatory cytokine upregulation at the LC. [Jpn J Physiol 54 Suppl:S213 (2004)]
