INHIBITION OF T-CELL SUPERANTIGEN RESPONSES FOLLOWING TREATMENT WITH THE KAPPA-OPIOID AGONIST U50,488H

Previous work in our laboratory has shown that cytokine production by primary murine macrophages, and macrophage cell lines, is inhibited fo llowing treatment with the kappa-opioid agonist U50,488H. Furthermore, we have found that the participation of both accessory cells and T ce lls in an antibody response is suppressed by this compound. We have ut ilized the superantigen staphylococcal enterotoxin B (SEB) to further examine the effects of U50,488H on accessory and T cell function. The results showed that the proliferative response of lymph node T cells t o SEB presented by activated macrophages was significantly inhibited b y the kappa-opioid agonist at concentrations as low as 100 nM. However , suppression of the T cell response to SEB presented by resting macro phages required 100 times the concentration of U50,488H. On the other hand, the production of IL-2 in response to lymph node T cell stimulat ion with SEB was not altered by the opioid treatment. Additional exper iments utilizing the opiate antagonist naloxone and the kappa-selectiv e antagonist nor-binaltorphimine (norBNI) were performed in order to f urther characterize the opioid receptor involved in the suppressive ac tivity of U50,488H. Results showed that both naloxone and norBNI were able to block the inhibitory activity of U50,488H. Further analysis sh owed that the proliferative response of thymic T cells was more sensit ive to the effects of U50,488H, and the response with both activated a nd resting macrophages was suppressed. In addition, the production of IL-2 by the thymic T cells was also inhibited by the opioid treatment. The mechanism of suppression of superantigen-induced T cell responses is discussed.