Hypothalamic pituitary adrenal axis and immune responses to endotoxin in rats with chronic adjuvant-induced arthritis.

We investigated the effect of immune challenge with LPS in both control rats and rats with adjuvant-induced arthritis (AA). Fourteen day-AA rats showed the expected activation of the hypothalamic-pituitary adrenal axis associated with increases in vasopressin mRNA and paradoxical decreases in corticotropin-releasing hormone (CRH) mRNA in parvocellular neurons of the hypothalamic paraventricular nucleus (PVN). However, following LPS there was an increase in both CRH and vasopressin mRNA in the PVN. Neither control rats nor rats with AA had measurable plasma levels of IL-6, but plasma levels of IL-1beta were 2.7-fold higher in AA animals. Following LPS injection both IL-1beta and IL-6 increased more markedly in AA than in control rats. Neither controls nor AA rats expressed IL-1beta or IL-6 mRNA in the brain. However, following LPS these were induced in the subfornical organ, choroid plexus, and median eminence of both groups of animals. The areas expressing IL-1b mRNA were larger in the AA animals and exhibited a punctate pattern throughout the brain parenchyma and PVN. These data reveal an increased peripheral and central immunological response to LPS during the chronic inflammatory process of AA, providing a mechanism through which inflammatory disease can influence the response to a novel immunological challenge.