Differential effects of systemic interleukin-1I2 on gene expression in brainstem noradrenergic nuclei

Aims: The cytokine, interleukin-1 beta (IL-1 beta ), is known to produce specific effects on the neuroendocrine system such as suppression of the reproductive axis and stimulation of the stress axis. The mechanism by which IL-1 beta produces these differential effects is not clear. Since norepinephrine (NE) is involved in these effects, we hypothesized that IL-1 beta acts on brainstem noradrenergic nuclei to affect gene transcription of NE synthesizing enzymes, cytokines and associated transcription factors. Main methods: Adult female Sprague Dawley rats in proestrus were divided into two groups. Control animals received PBS-BSA and the treatment group received 5 mu g of rat recombinant IL-1 beta i.p. at noon. They were sacrificed in groups at 1, 3 and 5 pm (n = 6/group) for measurement of tyrosine hydroxylase (TH) mRNA by qPCR or at 3 pm for mRNA analysis by qPCR array. Key findings: TH mRNA levels decreased gradually with time in both control and IL-1 beta -treated rats in the ventrolateral medulla. In the nucleus of solitary tract, TH mRNA levels were significantly reduced by IL-1 beta treatment at 5 pm. In the locus coeruleus, TH mRNA levels increased significantly at 5 pm with IL-1 beta treatment compared to controls. In the second set of animals analyzed by qPCR array, there were several fold increases in the expression of certain cytokines, chemokines, and transcription factors in specific noradrenergic nuclei. Significance: Systemic administration of IL-1 beta causes significant changes in the expression of tyrosine hydroxylase and several chemokines in brain stem noradrenergic nuclei, thereby mediating its neuroendocrine effects.