Morphine inhibits the development of allogeneic immune responses in mouse lymph node

Morphine and related opiates are often administered to relieve post-operative and chronic pain following transplantation surgery. Opiates have been shown to suppress a variety of immune parameters in both animal models and man. In the present study, we investigated whether morphine affects allogeneic immune responses by injecting C57BL/6 mice in the footpad with allogeneic spleen cells and examining changes in the draining popliteal lymph node (PLN). Morphine (administered as subcutaneous implants) had profound inhibitory effects on the development of alloreactivity manifested as a suppression of: (1) lymph node hyperplasia, (2) mixed lymphocyte reactivity (MLR) in PLN cells and (3) the number of CD4+ and Thy 1.2 lymphoid subsets. These inhibitory effects of morphine were abolished or dramatically reduced by co-administration of the opiate antagonist, naltrexone, indicating that suppression of allo-sensitization was opiate receptor mediated. In toto, these findings demonstrate that morphine administration interferes with the development of allogeneic immune response in mouse lymph node through an opiate receptor mediated mechanism.