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

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-1beta (IL-1beta) administration.

Objectives: Several peripheral and central effects of IL-1beta 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-1beta (1.0 microg) on plasma corticosterone and on circulating IL-1beta, IL-6, and TNF-alpha were diminished following 5-day IL-1beta treatment, although high levels of sickness were still apparent. When IL-1beta (1.0 or 2.0 mug/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-1beta 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-1beta infusion altered prefrontal cortical and hippocampal serotonin and norepinephrine utilization, and within these regions, the messenger RNA (mRNA) expression of IL-1beta, IL-6, TNF-alpha, and their receptors, as well as that of 5-HT(2C), 5-HT(1B) 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-1beta.