Interleukin-1 beta simultaneously affects the stress and reproductive axes by modulating norepinephrine levels in different brain areas.

Aims: Interleukin-1β (IL-1β) is a cytokine that is known to activate the stress axis and suppress the reproductive axis. Different brain areas are involved in the regulation of these two axes. However, they are both under the stimulatory control of the catecholamine, norepinephrine (NE). Here, we hypothesized that IL-1β differentially affects these two axes by modulating NE levels in specific brain regions.

Main Methods: Female Sprague-Dawley rats in proestrus were injected intraperitoneally with either PBS-1.0% BSA (control) or 5μg of IL-1β at 1pm. Groups of rats were sacrificed at 1, 3, and 5pm and their brains were collected. Brain areas associated with reproduction as well as areas associated with stress axis activity were isolated and analyzed for NE concentrations using HPLC-EC. Trunk blood was analyzed for IL-1β, corticosterone and luteinizing hormone levels.

Key Findings: As a general trend, treatment with IL-1β significantly decreased NE levels (p<0.05) in the areas controlling reproductive functions when compared to the control group. In contrast, NE levels increased significantly (p<0.05) in the stress associated areas. LH levels were markedly decreased with IL-1β treatment while corticosterone levels increased dramatically.

Significance: The ability of IL-1β to produce differential effects on the stress and reproductive axis could be explained by modulation of NE levels in specific brain areas that are associated with these functions. This differential regulation of NE may be an adaptive phenomenon in response to a systemic immune challenge.