Effect of rapamycin on repeated immobilization stress-induced immune alterations in the rat spleen

Chronic stress modulates immune system functions via neuroendocrine pathways. Rapamycin inhibits activity of immune cells through the mTOR signaling pathway. We investigated the effect of rapamycin (15 mg/kg, 3-times/week) on neuroimmune-endocrine system in the spleen of rats exposed to 42 cycles of 2-h immobilization. Rapamycin enhanced the activity of hypothalamic-pituitary-adrenocortical axis induced by stress exposure, prevented stress-induced expression of natural killer cell markers while reversed stress-evoked decline of Th2 immune response markers. Overall, our findings suggest that rapamycin may act on immune functions not only directly by inhibiting of mTOR in immune cells but also indirectly via modulation of neuroendocrine system.