Influence of Chronic Interleukin-2 Infusion and Stressors on Sickness Behaviors and Neurochemical Change in Mice

Abstract

Objectives: Major depression is associated with increased circulating interleukin-2 (IL-2) levels, and IL-2 immunotherapy may provoke depressive symptoms, leading to the suggestion that this cytokine may contribute to the evolution of affective disorders. Although depression is a relatively chronic condition, and immunotherapy involves repeated cytokine administration, animal studies have typically assessed the consequences of acute cytokine treatment. The present investigation assessed several behavioral and neurochemical effects of chronic IL-2 infusion. Methods: Behaviors reflecting anhedonia and/or anorexia, sickness behavior, plasma corticosterone and norepinephrine (NE) activity in the paraventricular nucleus (PVN) of the hypothalamus were assessed following continuous infusion of IL-2 over 7 days in CD-1 mice. Results: The cytokine treatment reduced the consumption of a highly favored palatable substance (chocolate milk) and reduced locomotor activity monitored over the course of the 7-day period. Although sickness behaviors were also increased significantly by the treatment, the degree of sickness behavior was actually modest. While a chronic, variable stressor also affected consumption of the palatable food, this treatment did not enhance the effects of IL-2. Furthermore, in contrast to acute and chronic stressors that increased plasma corticosterone levels and the utilization of NE within the PVN of the hypothalamus, IL-2 did not promote such effects and did not modify the impact of the stressors. Conclusion: While IL-2 may induce anorexia or anhedonia, the effects of this treatment are distinguishable from those elicited by stressors and those typically elicited by proinflammatory cytokines. The data are related to findings suggesting a link between IL-2 and depressive illness.

Neurobiology of chronic mild stress: Parallels to major depression

“…In contrast, one study reported an elevation in whole hypothalamic levels of NE (Prieto et al, 2003) and two others have reported elevations in NE utilization within the PVN (Patterson et al, 2010; Sudom et al, 2004). The primary differences among these studies is that for the whole hypothalamic assay, the analysis was performed 24 h following the final stressor, whereas in the study by Haidkind et al (2003), analysis was done 7 days following the final stressor, suggesting that a recovery of function may have occurred during this period.…”

“…When specific subregions of the hypothalamus are examined, there appears to be great consistency of results. In general, data suggest that there is no effect of CMS on serotonergic transmission in the paraventricular nucleus of the hypothalamus (Tannenbaum and Anisman, 2003; Sudom et al, 2004; Tannenbaum et al, 2002; Patterson et al, 2010), while in the median eminence, CMS has been reported to increase 5-HT utilization (Tannenbaum and Anisman, 2003). The only published study to date that has examined 5-HT receptor binding in the hypothalamus following CMS reported reduced 5-HT 1A receptor binding following CMS (Jang et al, 2004).…”

Chronic Mild Stress (CMS) Revisited: Consistency and Behavioural-Neurobiological Concordance in the Effects of CMS

“…These include two series of studies reporting a decreased intake of palatable food intake in brief (3 or 5 min) sessions in rats [89,95,96,98] , and a similar effect in mice [82,97] , and one study that actually reported an increase in total intake of palatable food, but in the context of a very slow rate of eating in a much longer (30 min) session [98] . In the studies by Di Chiara and colleagues [100,101] , the dependent measure was dopamine release in nucleus accumbens shell and prefrontal cortex in response to the taste of a palatable food: these measures were both decreased by CMS.…”

Inflammatory Cytokines and Antipsychotic-Induced Weight Gain: Review and Clinical Implications

“…The anorexigenic outcomes of the APR can be mimicked by externally administering inflammatory cytokines to the periphery or CNS, with synergistic effects occurring between cytokines in some cases [78,79,80,81,82,83,84,85,86]. The resultant alterations in feeding behaviours are typically observed as reductions in meal size, duration, and frequency, and longer inter-meal intervals [80,85,87].…”