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Influence of continuous infusion of interleukin-1β on depression-related processes in mice: corticosterone, circulating cytokines, brain monoamines, and cytokine mRNA expression

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Abstract

Rationale

Activation of the immune system typically occurs on a subchronic or chronic basis (e.g., in response to bacterial or viral insults). However, analyses of the effects of cytokine treatments have typically involved acute treatments, and limited data are available concerning the behavioral and central neurochemical impact of subchronic interleukin-1β (IL-1β) administration.

Objectives

Several peripheral and central effects of IL-1β treatment were assessed following single or repeated bolus injections or after infusion of the cytokine (through Alzet minipumps) over several days.

Results

The impact of an acute bolus injection of IL-1β (1.0 μg) on plasma corticosterone and on circulating IL-1β, IL-6, and TNF-α were diminished following 5-day IL-1β treatment, although high levels of sickness were still apparent. When IL-1β (1.0 or 2.0 μg/day) was continuously infused over 3 days, plasma corticosterone and sickness were elevated, but these effects were attenuated after 7 days (subchronic) of treatment. As well, the effects of IL-1β treatment on diurnal variations of motor activity diminished over days. Despite the diminution of the behavioral and neuroendocrine effects of the cytokine after treatment 7 days, subchronic IL-1β infusion altered prefrontal cortical and hippocampal serotonin and norepinephrine utilization, and within these regions, the messenger RNA (mRNA) expression of IL-1β, IL-6, TNF-α, and their receptors, as well as that of 5-HT2C, 5-HT1B receptors, and p11, was increased.

Discussion

The findings indicate that peripheral cytokine infusion markedly influences central cytokine mRNA expression and also influences 5-HT turnover, which might contribute to behavioral changes elicited by IL-1β.

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Authors and Affiliations

  1. Institute of Neuroscience, Carleton University, Ottawa, ON, K1S 5B6, Canada

    Hymie Anisman, Julie Gibb & Shawn Hayley

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  1. Hymie Anisman
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  2. Julie Gibb
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Correspondence to Hymie Anisman.

Additional information

The research was supported by the Canadian Institutes of Health Research (CIHR) and by the Canada Foundation for Innovation (CFI). Hymie Anisman and Shawn Hayley hold Canada Research Chairs in Behavioral Neuroscience and in Neuroscience, respectively. None of the authors have a financial interest in either CIHR or CFI.

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Anisman, H., Gibb, J. & Hayley, S. Influence of continuous infusion of interleukin-1β on depression-related processes in mice: corticosterone, circulating cytokines, brain monoamines, and cytokine mRNA expression. Psychopharmacology 199, 231–244 (2008). https://doi.org/10.1007/s00213-008-1166-z

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  • DOI: https://doi.org/10.1007/s00213-008-1166-z

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