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−1β were 2.7−fold higher in AA animals. Following LPS injection both IL−1β and IL−6 increased more markedly in AA than in control rats. Neither controls nor AA rats expressed IL−1β 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 challeng

Expression of interleukin-1 beta in rat dorsal root ganglia

The expression of interleukin-lp was examined in dorsal root ganglion (DRG) neurons from adult rats using non-radioactive in Situ hybridization and immunocytochemistry. At all spinal levels, approximately 70% of the DRG neurons appeared to express IL-1 beta mRNA: about 80% of these DRG neurons actually appeared to produce the IL-lp protein at markedly varying levels. The expression of IL-1 beta was found in large as well as in intermediate diameter sensory neurons but only sporadically in the population of small sensory neurons. The population of IL-1 beta immunopositive sensory neurons included most of the large calretinin-positive la afferents. but only a few of the small substance P/CGRP positive sensory neurons. In situ hybridization staining for the detection of type 1 IL-1 beta receptor showed expression of this receptor by most of the sensory neurons as well as by supportive glial-like cells, presumably satellite cells. The functional significance of IL-1 beta in the DRG neurons needs to be elucidated, but we speculate that IL-1 beta produced by DRG neurons may be an auto/paracrine signalling molecule in sensory transmission. (C) 2001 Elsevier Science B.V. All rights reserved