Cachectin/Tumor Necrosis Factor and the Pituitary-Adrenal Axis

Results from our studies investigating immune-neuroendocrine interactions have yielded interesting and novel findings. In unanesthetized rats, TNF 10ugkg was a potent stimulus for ACTH release without affecting hemodynamics. In vitro, TNF was without effect on the basal secretion of corticosterone CS but inhibited ACTH-stimulated CS release. Likewise, TNF inhibited TSH-stimulated thyroglobulin release from cultured human thyroid cells. In vitro, ACTH tended to inhibit LPS-induced TNF release from cultured macrophages, however, in the presence of serum-free media, ACTH appeared to potentiate TNF release. Also, the dose-response curves for CS and dexamethasone inhibitors of TNF release were shifted to the right. Together these findings suggest that factors present in sera and absent in serum-free media may interfere with LPS binding andor uptake into macrophages. Results from these studies have provided additional knowledge and insight into the bidirectional communication between the neuroendocrine and immune systems. Keywords Tumor necrosis factors Cachectin ACTH Corticosterone thyroglobulin Macrophage LPS Dexamethasone cAMP Cyclic adenosine monophosphate Monokines Cytokines.