ストレス免疫応答における脳内メディエーターとしてのプロスタグランディンE2

抄録

Several lines of evidence have suggested that prostaglandin E₂ (PGE₂) is one of the intermediate messengers between the brain and immune system in, e.g., the infection-induced fever and endocrine responses. In the present study we investigated an involvement of PGE₂ in the immobilization (IMB, 1 hr)-induced suppression of splenic natural killer (NK) cell activity and its hypothalamo-sympathetic mechanisms. Intracerebroventricular (ICV) injection of a cyclooxygenase inhibitor, diclofenac (1 μg/1 μl saline, 15 min before IMB), partially blocked the IMB-induced suppression of NK activity in rats. In addition, diclofenac inhibited the IMB-induced expression of Fos protein in the hypothalamic paraventricular nucleus (PVN). An ICV injection (1 μg/l μl) of PGE₂ suppressed NK activity, while microinjection (0.1 μg/0.1 μl) study showed that the acting sites of PGE2 were the medical preoptic hypothalamus (MPO) and PVN, but not the ventromedial hypothalamus. Interestingly, microinjection of PGE₂ into the lateral hypothalamic area enhanced NK activity. We have shown that an activation of the splenic sympathetic nerve (SSN) induces a suppression of splenic NK activity, and ICV injection of PGE₂ increased SSN activity through EP₁ receptors. In accordance with these and present findings, microinjection of PGE₂ into the MPO and PVN, but not VMH, increased SSN activity, while the LHA injection decreased the SSN activity. These findings, taken together, suggest that hypothalamic PGE₂ plays a role in the stress-induced immunomodulation. [J Physiol Sci. 2007;57 Suppl:S115]