Beta-endorphin stimulates Ia expression on mouse B cells by inducing interleukin-4 secretion by CD4+ T cells

In the present study we show that the opioid peptide beta-endorphin (beta-End) enhances Ia expression on murine B cells in cultures of unseparated spleen cells, mediated by low concentrations of IL-4 in the absence of antigenic or mitogenic stimulation. Since this effect was not found with purified B cells and no enhancement of IL-4 receptor expression on B cells could be observed, we studied the effect of beta-End on IL-4 production. To this end, purified CD4+ T cells were stimulated with suboptimal concentrations of Con A in the presence of irradiated spleen cells. It was indeed shown that beta-End enhances IL-4 production. To establish the role of macrophages in this process, we measured IL-1 and IL-6 production under the influence of beta-End. Splenic adherent cells as well as peritoneal macrophages produced higher levels of IL-1 and IL-6 in response to beta-End, whereas IL-1 was shown to enhance Ia expression similar to beta-End. Using anti-IL-6 it was demonstrated that IL-6 was required for the stimulation of Ia expression by beta-End. It is concluded that a local increase in beta-End may result in upregulation of Ia expression on B cells, thereby most likely improving their antigen-presenting capacity.