Cytokine and adrenal axis responses to endotoxin.
The push-pull cannula (PPC) technique was applied to examine the kinetics of in vivo concentration changes in male rat brain extracellular fluid (ECF) of endogenous interleukin-1beta (IL-1beta) and corticotrophin releasing hormone (CRH) after a peripheral injection of lipopolysaccharide (LPS) (25 microg/100 g b.wt. intravenously). In addition, IL-1beta, adrenocorticotropin hormone (ACTH) and corticosterone concentrations in plasma were also measured at selected intervals after LPS challenge. Administration of LPS resulted in a progressive increase in the concentrations of IL-1beta in brain hypothalamic ECF. A significant increase from the zero time mean value of 77+/-10 to 393+/-88 pg/ml at the 15-min interval was recorded. The increase in IL-1beta concentration in hypothalamic ECF reached a peak of 883+/-237 pg/ml at 30 min post-LPS. CRH concentration in the same hypothalamic ECF was 41+/-17 pg/ml at time zero, 97+/-15 pg/ml at 15 min and at 30 min was significantly increased (215+/-56 pg/ml). A time course of significant increases at 30 min in plasma concentrations of IL-1beta, ACTH and corticosterone was also recorded in the same animals described above. The data show that a peripherally administered LPS bolus elicited an early (over 15 min post-injection) increase in brain ECF IL-1beta concentration; additional significant increases in hormones released from the hypothalamic-pituitary-adrenal (HPA) axis were recorded at 30 min post-LPS injection. These observations support the concept of an early change in hypothalamic ECF concentration of IL-1beta preceding LPS-induced activation of the HPA axis.
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Department of Anatomy, College of Medicine, University of South Florida, Tampa, FL 33612-4799, USA.
Chen
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Oliver
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Horvath
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Phelps
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CP
D000324:Adrenocorticotropic Hormone / Q000097:blood* / Q000187:drug effects; D000818:Animals; D003345:Corticosterone / Q000097:blood*; D003346:Corticotropin-Releasing Hormone / Q000187:drug effects / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D004731:Endotoxins / Q000494:pharmacology; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects* / Q000378:metabolism; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism*; D007375:Interleukin-1 / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D010913:Pituitary-Adrenal System / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D016207:Cytokines; D004731:Endotoxins; D007375:Interleukin-1; D008070:Lipopolysaccharides; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D003345:Corticosterone