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Injection of mice with an additional dose of LPS at 4 h resulted in no further increase in serum TNF. The <jats:italic>in vivo<\/jats:italic> kinetics of TNF appearance correlated with <jats:italic>in vitro<\/jats:italic> studies in which TNF mRNA was detected in murine peritoneal macrophages 30 min after LPS stimulation. The increase in serum TNF was not detected in mice treated with dexamethasone, 3 mg\/kg, prior to LPS stimulation. The decrease in TNF correlated with the appearance of significant amounts of endogenous serum corticosterone which were maximal by 3 h. Further evidence for the role of endogenous steroids in the modulation of serum TNF levels was obtained in studies with adrenalectomized or hypophysectomized mice. Compared to sham\u2010operated animals, serum TNF levels remain elevated 5 h post LPS stimulation in adrenalectomized or hypohysectomized mice. In contrast with the transient increase in TNF, serum IL 1 was maximal 4 h post LPS injection and remained elevated at 24 h. <jats:italic>In vitro<\/jats:italic> studies with primary cultures of human peripheral blood monocytes and human umbilical cord vein endothelial cells demonstrated that LPS\u2010induced mono\u2010cyte IL 1 levels were reduced approximately 5\u2010fold by 10<jats:sup>\u20101<\/jats:sup> M dexamethasone while dexamethasone had only minimal effects on endothelial cell IL 1. Therefore, the <jats:italic>in vitro<\/jats:italic> data would suggest that the maintenance of elevated IL 1 levels coincident with the appearance of endogenous corticosteroids during LPS shock is related to the synthesis of IL 1 by both monocyte\u2010macrophages and non\u2010myeloid cell populations including endothelial cells.<\/jats:p>","DOI":"10.1002\/eji.1830190213","type":"journal-article","created":{"date-parts":[[2007,3,1]],"date-time":"2007-03-01T10:41:59Z","timestamp":1172745719000},"page":"301-305","source":"Crossref","is-referenced-by-count":240,"title":["Differential regulation of lipopolysaccharide\u2010induced interleukin 1 and tumor necrosis factor synthesis: effects of endogenous and exogenous glucocorticoids and the role of the pituitary\u2010adrenal axis"],"prefix":"10.1002","volume":"19","author":[{"given":"Steven H.","family":"Zuckerman","sequence":"first","affiliation":[]},{"given":"James","family":"Shellhaas","sequence":"additional","affiliation":[]},{"given":"Larry D.","family":"Butter","sequence":"additional","affiliation":[]}],"member":"311","published-online":{"date-parts":[[2005,12,6]]},"reference":[{"key":"e_1_2_1_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/0167-5699(86)90124-6"},{"key":"e_1_2_1_3_2","doi-asserted-by":"publisher","DOI":"10.1159\/000169542"},{"key":"e_1_2_1_4_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198702123160705"},{"key":"e_1_2_1_5_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/157.3.413"},{"key":"e_1_2_1_6_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.107.4.1269"},{"key":"e_1_2_1_7_2","first-page":"668","volume":"110","author":"Movat H. 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