抄録
Microglial cell has been demonstrated to be involved in various diseases, such as Alzheimer and Parkinson diseases, HIV encephalitis and multiple sclerosis. In spite of the facts that stress plays crucial roles in the progression of clinical diseases, the involvement of stress on the microglial activity remains to be elucidated. Based on finding that stress induced the elevation of proinflammatory cytokines, we hypothesized; (1) physical/emotional stress may have some effect on the microglial activation, (2) IL-18, a proinflammatory cytokine and demonstrated to be increased in stress from the adrenal gland, may participate in the microglial activation. We employed restraint combined with water immersion stress for 2 hours as acute stress. Immediately after release from stress, rats were sacrificed for experiments. Immunohistochemistry with OX-42 revealed that acute stress provoked morphological microglial activation in the thalamus, hypothalamus, hippocampus and central grey. Semi-quantitative real time PCR and immunohistochemistry showed that stress significantly induced IL-6 and iNOS from microglia. In addition, intraperitoneal IL-18 administration (5 μg/rat) caused robust microglial activation in the brain in a similar fashion observed in stress. Furthermore, in-vitro studies using microglia cell line (MG6-1) demonstrated that IL-18 administration (up to 500 ng/ml) significantly induced iNOS, IL-6, and IL-18 in a dose dependent manner. Thus, the present study suggests that stress may stimulate microglial cells to produce several pro-inflammatory cytokines and iNOS at least through stress-induced circulating IL-18. [J Physiol Sci. 2006;56 Suppl:S105]
