Diazepam improves the functional disorder of the alveolar macrophage caused by chronic stress in mice

S Ichida, Y Funakami, C Wakaki, K Ueshiba, M Nakao, K Sakai, T Wada. Division of Biochemistry, Kinki University Faculty of Pharmacy, Higashi-Osaka, Osaka, Japan

The immunity controlled by the autonomic nervous system (ANS) is attenuated by stress (1). It is known that the stress also affects ANS. The specific alternation of rhythm in temperature (SART)-stressed mice which have various chronic stress symptoms is considered a model for autonomic imbalance (2). It is supposed that the function of immunity in this animal decreases. The aim of this study was to investigate the relationships between stress and immunity using alveolar macrophages (Mφ s) of SART-stressed mice.

Male ddY mice (n=6-10) were administered diazepam (Dz) at 4mg/kg/day, p.o. during the stress loading as follows. Mice were transferred between 24°C room’s cage and 4°C room’s cage hourly from 9:00 to 16:00 and housed in a cage at 4°C from l6:00 to 09:00 the following morning. This procedure was repeated for 8 days up to 11:30 on the final day. The bronchoalveolar lavage fluid (BALF) was obtained by washing lungs with phosphate-buffered saline under urethane (1.5 g/kg, i.p.) anesthesia. Mφ s w ere obtained from the pellet by centrifugation of BALF. The Mφ s phagocytosis and BALF cytokine production were examined.

Phagocytotic activity and the concentration of BALF cytokines, TNF-α, IL-1β, in SART-stressed mice were significantly decreased in comparison with those in non-stressed mice. Dz treatment blocked these phenomena as shown in phagocytotic activity (Fig.1a) and BALF Cytokines (Fig.1b) in SART-stressed mice.

Fig. 1 Effect of Dz on phagocytotic activity of Mφs (Fig. 1a) and BALF cytokines (Fig. 1b) in SART-stressed mice. Non-stressed (□) and SART-stressed (▪) mice. ***p<0.01, *p<0.05 v.s. the respective non-stress group. ##p<0.01 v.s. the respective vehicle treated group (Tukey’s test).

In summary, SART stress decreases the immune function of Mφs such as phagocytosis and cytokine production. These abnormalities were improved by the antianxiety drug, Dz. These results suggest that chronic stress reduces the function of the Mφ which plays an important role in immunity through ANS.

(1) Hanke ML, Powell ND, Stiner LM, et al. (2012) Brain Behav Immun 26: 1150-1159.

(2) Hata T, Kita T, Itoh E, et al. (1983) Jpn J Psychosom Med 23: 61-68.