MORPHINE-INDUCED ALTERATIONS IN ANTIBODY-LEVELS - RECEPTOR AND IMMUNE-MECHANISMS

We have previously shown that an acute administration of morphine (10 mg/kg, i.v.) decreases IgG, but not IgM, antibody levels to antigen ad ministered before morphine. Further, decreases in IgG were blocked by previous administration of naltrexone, indicating that receptor bindin g is critical to the decreased antibody levels. These studies investig ated potential receptor and immune mechanisms for these effects. To in vestigate potential receptor mechanisms, the stereoselectivity and loc ation of receptor binding was determined. The results of these experim ents suggest morphine must bind stereoselectively to central sites to decrease antibody levels after antigen administration. To investigate potential immune mechanisms for these changes, antibody secreting cell s (ASC) for keyhole limpet hemocyanin-specific IgG and IgM were enumer ated. Morphine decreased ASC for IgG but increased ASC for IgM. Two pa thways for the genetic switch from IgM to IgG production were investig ated. One pathway requires interferon-gamma to stimulate IgM-secreting cells to switch to IgG2a-secreting cells. Another pathway requires in terleukin-4, to stimulate IgM-secreting cells to switch to IgG1- secre ting cells. IgG1 and IgG2a levels were measured to determine if these pathways were differentially affected and only IgG2a levels were decre ased. Further, these decreases were accompanied by decreased IFN-gamma levels but not by altered numbers of splenocytes. These data indicate that morphine may alter the ability of ASC to switch from IgM to IgG2 a production, possibly by reducing the availability of IFN-gamma.