Endotoxin induced increases in rat plasma pituitary-adrenocortical hormones are better reflected by alterations in tumor necrosis factorα than interleukin-1β

Abstract

In order to assess the relative cytokine contribution to endotoxin stimulation of pituitary-adrenocortical hormone secretion, we measured plasma levels of interleukin-1β (IL-Iβ), tumor necrosis factorα (TNFα), adrenocorticotropin (ACTH) and corticosterone following lipopolysaccharide (LPS) challenge in rats. LPS administration induced robust increases in both plasma ACTH and corticosterone levels at 3 h after i.p. injection; while ACTH decreased towards control levels, corticosterone remained at peak concentrations at 6 h after LPS injection. Basal levels of plasma IL-1β were below the sensitivity of the ELISA and basal levels of plasma TNFα were 0.25 ± 0.12 pM. Small but highly variable non-significant increases in plasma IL-1β levels were seen at 3 h and 6 h after injection of LPS. The lack of functional consequences of the small increases in IL-1β levels was demonstrated by unchanged levels of [ 125I]IL-1α binding in liver at 3 h after LPS injection. In contrast, dramatic increases in plasma TNFα concentrations were observed at 3 h and decreased to non-injected control levels at 6 h after LPS injection. There was a significant positive correlation between ACTH and TNFα after LPS injection, while no correlation was seen between ACTH and IL-1β. These data demonstrate differential regulation of IL-1β and TNFα by endotoxin treatment and suggest that TNFα may be a more potent mediator of LPS-induced ACTH secretion in rat.