Morphine affects the brain-immune axis by modulating an interleukin-1 beta dependent pathway

Abstract

In the neuroendocrine system, chronic exposure to morphine causes a desenstitization of FOS responsiveness in the PVN, and may impair the HPA axis by attenuating IL-1β-induced FOS activation and CRF expression in the PVN. In the immune system, chronic exposure to morphine attenuates the LEA response in the FML P-induced acute inflammatory condition, which may contribute to the suppression of the immunological response. However, in response to systemic challenge with 1L-1β, chronic exposure to morphine potentiates the LEA response to IL-1β. This may reflect the impairment of the HPA axis in the rats given chronic morphine. The modulatory loop in the brain-immune axis may be interrupted by chronic exposure to morphine, as shown in Figure 2. In this model, chronic exposure to morphine could attenuate the IL-1β-stimulated release of ACTH and glucocorticoids, which serve in an inhibitory feedback loop on immunological responses, such as LEA. In conclusion, our studies suggest that morphine interrupts the brain-immune axis by modulating an IL-1β-dependent pathway.