Interactions of immune and neuroendocrine systems in response to the superantigen staphylococcal enterotoxin B

Abstract

The Immune and neuroendocrine systems interact with each other through cytokines and hormones. Staphylococcal enterotoxin B (SEB) is a powerful inducer of cytokines. The present studies were conducted to investigate the effect of SEB on the interaction between the immune and neuroendocrine systems. In monkeys challenged with SEB, efforts were made to investigate the interrelationships among the circulating cytokines, lymphoid cells, ACTH, and glucocorticoids (GCs). It was found that in dying monkeys there was an increase of cytokines (TNF, IL-2, IL-6, and IFN-gamma) that paralleled the appearance of ACTH and GCs and various lymphocyte subpopulations. To further study the complicated interactions among cytokines, lymphoid cells, and GCs, lymphoid cell cultures were established and stimulated with SEB, SEB plus dexamethasone (DEX), or SEB plus cytokines. DEX, if added after SEB to lymphoid cell cultures, generally suppressed SEB-induced mitosis. However, if DEX was added simultaneously with SEB, it enhanced SEB-induced mitosis of spleen cell cultures but not of lymphocytes from other lymphoid tissues. The enhancement appeared to be regulated primarily by IL-1 and to a lesser extent by IL-6. The significance of DEX-enhanced SEB-induced mitosis was further studied in mice challenged with SEB, or SEB plus DEX. Spleen cells from these mice were stimulated in culture with SEB, SEB plus DEX, and SEB plus cytokines. It was found that spleen cells from mice challenged with SEB or SEB plus DEX became tolerant to SEB-induced mitosis in culture. Because there were increases in the total number of splenic T cells and of Vbeta8 T cells, which are normally SEB-reactive, this tolerance appeared to be due to anergy rather than cell depletion. The anergic state of these cells could not be overcome by adding DEX and various cytokines to the lymphoid cell cultures. In conclusion, SEB may affects the interaction of the immune and neuroendocrine systems through the production of large amounts of cytokines that act on the neuroendocrine system which, in turn, releases ACTH and then GCs which subsequently regulate the immune system. The increased levels of cytokines and GCs may result in an over-stimulation of the nervous and immune systems resulting in pathophysiological changes of various organs and organ systems. A profound effect of GCs and SEB on the immune system is the development of anergy, which may confer resistance to subsequent SEB insult.