Predator exposure-induced cerebral interleukins are modulated heterogeneously by behavioral asymmetry

Predator exposure is a naturalistic stressor that is likely to elicit a stressful response pattern similar to those experienced in the real world. As a consequence of stress, HPA hormonal activity and the alteration of mediators such as cytokines may result. Behavioral asymmetry, as assessed by paw preference, exerted effects on immune responses and peripheral cytokine production, observed after exposure to the physical stimuli. Thus, we hypothesized that behavioral asymmetry can modulate mouse brain interleukins and HPA activity after exposure to an internally generated psychological stress source. To determine the impact of behavioral asymmetry, mice were divided into left- and right-pawed groups by paw preference. Then, the mice received either a single 60-min or a daily 60-min predator exposure (cat exposure) for 14 consecutive days. After receiving predator exposure, trunk blood was collected and brain tissues, including the cerebral cortex, hippocampus and hypothalamus, were separated. Plasma corticosterone (CS) was detected by EIA, and IL-1β and IL-6 levels in the cortex, hippocampus and hypothalamus, were quantified by ELISA. The results revealed that predator stress, in particular chronic stress, could enhance plasma CS concentration and could alter IL-1β and IL-6 concentrations in the cortex, hippocampus and hypothalamus. Simultaneously, predator stress-induced CS and brain interleukin levels were modulated by behavioral asymmetry. The left-pawed mice showed a decreased variation in CS, less than right-pawed mice, and both left-pawed and right-pawed mice displayed heterogeneous direction and intensity of changes for IL-1β and IL-6 in the cortex, hippocampus and hypothalamus after predator exposure. From these results, it can be concluded that the alteration of cytokines depends on the characteristics of the stressor. Furthermore, the asymmetric cytokine responses within the brain to a natural, psychological stressor may be involved in the immunomodulation of behavioral asymmetry. These findings likely reflect the flexibility in reactivity patterns of a population in response to various insults.