ASSESSMENT OF IMMUNOTOXICITY OF BUPRENORPHINE

In order to use buprenorphine as an analgesic in immunological experim ents, we have studied the potential immunotoxicity of buprenorphine. T hree-week-old male Wistar Riv:TOX rats were subcutaneously treated wit h buprenorphine by injection of 0.1, 0.4, or 1.6 mg/kg body weight per day over a period of 4 weeks. Concentrations used were within the ran ge for analgesia in rats. A slight decrease of body weight gain was ob served at the highest dose in one but not in a duplicate study. Decrea sed liver weights were observed in all dose groups. Histopathologicall y glycogen storage was decreased and fatty vacuolation was found to be increased starting from the lowest dose group. The relative but not a bsolute weight of the lungs was slightly increased at the lowest dose, this phenomenon was therefore not dose-dependent. Histopathologically , a dose-dependent increase in interstitial pneumonia in the lung was found. At the 2 higher dose levels the weight of the adrenal glands wa s increased. No haematological changes were found, nor were there effe cts on bone marrow. In one of 2 studies indications of potential immun otoxicity noted were: an increased weight of the thymus, as well as an increased weight of popliteal and mesenteric lymph nodes. No effects on the weight of the spleen were found. Histologically, there were no changes in the lymphoid organs tested. Total immunoglobulin A concentr ations in serum were significantly decreased in the highest dose group , whereas IgG concentrations were increased, albeit not statistically significantly. IgM and IgE concentrations showed no alterations. Two t ypes of immune function assays were carried out: determination of natu ral killer cell activity and of mitogen responsiveness of spleen cells . Whereas natural killer activity was unaffected, increased responses to concanavalin-A, phytohaemagglutinin, pokeweed mitogen as well as li popolysaccharide were found, although never statistically significant. The results indicate that buprenorphine may have a slight stimulatory influence on the immune system at dose levels that are used for analg esia. The effects on the immune system that were noted were modest. Mo reover, they were observed in conjunction with other toxicological eff ects, and can therefore either be direct or indirect.