Chronic Mild Stress in Mice Decreases Peripheral Cytokine and Increases Central Cytokine Expression Independently of IL-10 Regulation of the Cytokine Network

Abstract

Objectives: Accumulating evidence indicates that stress leads to an increased expression of pro-inflammatory cytokines such as interleukin (IL)-6. The production and action of pro-inflammatory cytokines are down-regulated by anti-inflammatory cytokines such as IL-10. This makes IL-10-deficient mice a potentially useful model to assess the effects of stress on cytokine production. Methods: In the present study, IL-10-deficient mice were compared to wild-type mice in their behavioural and cytokine response to a chronic mild stress procedure. Results: The 3-week chronic mild stress decreased body weight gain and sucrose consumption. It also resulted in a decreased expression of peripheral IL-1β and IL-6 and an increased expression of brain IL-6. This last change in IL-6 was correlated to body weight loss in stressed mice. However, IL-10-deficient mice did not differ from wild-type mice in their response to the chronic mild stress procedure, despite substantial differences in functioning of the cytokine network. Conclusion: These results are interpreted in the context of the relationship between cytokines and behaviour.

Chronic Variable Stress Alters Inflammatory and Cholinergic Parameters in Hippocampus of Rats

“…We observed that chronic stress provoked an increase in the levels of IL-1b, IL-6 and TNF-a, but did not alter the level of chemokine MCP-1. These results are in agreement with those of other investigators who demonstrated an increase in inflammatory markers in the hippocampus of rats submitted to different stress regimens [4,[46][47][48].…”

Integrating Interleukin-6 into depression diagnosis and treatment

“…Rodents exposed to chronic mild stress (CMS), a series of stressors presented in an unpredictable manner over time, express anhedonia and increased circulating levels of pro-inflammatory cytokines including IL-6 (Pan et al., 2006, Mutlu et al., 2012). It should be noted some studies have found no significant change (Farooq et al., 2012) or even a decrease in peripheral IL-6 (Mormede et al., 2002) following CMS. However, both of these studies found increased brain levels of other inflammatory markers and may reflect a time-dependent shift from peripheral to central cytokine activation or even potentially transport of the peripheral cytokines into the brain (Mormede et al., 2002, Farooq et al., 2012).…”

Neuroinflammatory Mechanisms Linking Pain and Depression

“…WKY rats exhibit increased astrocyte expression in the dorsal raphe nuclei [75] and reductions in astrocyte expression in the PFC and amygdala [76]. Microglial activation and increased protein levels of proinflammatory cytokines has been reported following chronic/social stress in the PFC, PAG, amygdala and hippocampus [77][78][79] and OB rats exhibit increased IL-1β, TNFα, prostaglandins and astrocyte activation in the brain [80][81][82][83]. Therefore, models of depression exhibit region-specific alterations in glial activation in sites implicated in emotional and pain processing, effects which may contribute to the altered nociceptive responding in these models of depression.…”