Role of macrophage cytokines in mucosal adjuvanticity.

Delivery of protein antigens to the GALT can result in immunity or oral tolerance depending on the circumstances of the encounter. One mechanism by which mucosal adjuvants can affect these circumstances is by the induction of macrophage cytokines, including IL-1 and IL-12. These cytokines can directly affect the immune response by their effects on antigen-specific T cells and by the induction of IFN-gamma by T cells or NK cells. This IFN-gamma also activates macrophages to up-regulate MHC or costimulatory molecules and by further inducing IL-1 and IL-12. In effect, mucosal adjuvants function both directly and indirectly as activators of antigen presenting cells, resulting in stimulation of the immune response to coincidental antigens. Our studies in swine have shown CT is a potent mucosal adjuvant for CT-B. CT also increased IL-1 and IL-12 mRNA in cultured macrophages, especially after activation with IFN-gamma. The effect of CT on the secretion of bioactive IL-12 protein is currently being investigated. While the mucosal adjuvanticity of CT involves a variety of mechanisms, these findings suggest a role for the induction of the macrophage cytokines IL-1 and IL-12.