Selective Depletion of Macrophages Prevents Pituitary-Adrenal Activation in Response to Subpyrogenic, but not to Pyrogenic, Doses of Bacterial Endotoxin in Rats*

作者：Roel H. DeRijk, Nico van Rooijen, Fred J.H. Tilders, Hugo O. Besedovsky, Adriana del Rey, FRANK BERKENBOSCH · 发表于：Endocrinology · 年份：1991 · DOI：10.1210/endo-129-1-330 · 被引用次数：112 · 研究领域：Stress Responses and Cortisol、Adrenal Hormones and Disorders、Immune Response and Inflammation

The mechanisms by which bacterial endotoxin [lipopolysaccharide (LPS)] stimulates the hypothalamo-pituitary-adrenal axis (HPAA) have not been elucidated. The present study was designed to investigate the involvement of macrophages in plasma ACTH and corticosterone responses to LPS administration in rats using selective in vivo macrophage depletion. Intraperitoneal administration of subpyrogenic doses of LPS to normal rats resulted in elevated plasma ACTH and corticosterone concentrations, measured 2 h later. The response showed a remarkable steep dose relationship, with minimal effective doses between 0.5-1.5 micrograms (ACTH) and 0.5 micrograms or less (corticosterone)/kg BW. Plasma PRL, LH, and catecholamine (norepinephrine, epinephrine) levels were not significantly changed under the conditions used. Only at 6 h after LPS administration was a small elevation of norepinephrine noted. To deplete macrophages, rats were injected with liposomes encapsulated with dichloromethylene diphosphonate (Cl2MDP). Histochemical (acid phosphatase) and immunocytochemical techniques (monoclonal antibodies to rat macrophages coded ED1 and ED3) were applied to examine the efficiency of macrophage elimination by the Cl2MDP liposomes in cytospins of peritoneal exudates and in sections of the liver and spleen. Since cells of the macrophage lineage are considered to be the main source of IL-1 in the circulation, we also measured circulating levels of immunoreactive interleukin-1 beta (IL-1) concen...