Synergistic and antagonistic actions of acute or chronic social stressors and an endotoxin challenge vary over time following the challenge.

Acute stressor exposure and immunogenic challenges can synergistically increase behavioral, endocrine and neuroinflammatory responses, but much less is known about how chronic stressors influence the actions of immune challenges. In the present investigation we assessed the influence of bacterial endotoxin, lipopolysaccharide (LPS), administered on an acute chronic stressors backdrop, on sickness behavior, changes of circulating corticosterone and cytokine levels, and cytokine mRNA expression in the prefrontal cortex (PFC) and hippocampus. In this regard, it was of particular interest to determine whether the stressors would alter the temporal biological effects (onset and normalization) of LPS. There was a leftward shift in the temporal curve, in that sickness behavior, corticosterone and plasma IL-6 elevations among stressed mice appeared sooner after LPS treatment, but 3h after treatment corticosterone and IL-6 were lower than in nonstressed mice. In contrast, the stressor, especially when applied chronically, diminished the effects of LPS on TNF-α over the course of measurement, whereas effects on IL-10 were enhanced. In contrast to these peripheral effects, central cytokine mRNA expression, especially IL-1β and TNF-α, were diminished 1.5h following stressor and LPS administration, but were then synergistically enhanced at 3h compared to non-stressed controls. Although acute and chronic stressors provoked similar behavioral and neuroendocrine responses when combined with LPS, the effects of chronic stressors and LPS on brain cytokines were generally diminished, particularly in the PFC. The implications of the temporal changes related to stressors and immune activation are discussed, and several possible mechanisms for these effects are suggested. Crown