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      Cytokine Regulation of Corticosteroid Receptors in the Rat Hippocampus: Effects of Interleukin-1, Interleukin-6, Tumor Necrosis Factor and Lipopolysaccharide

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          The effects of interleukin-1β (IL-1), interleukin-6 (IL-6), tumor necrosis factor α (TNF) and lipopolysaccharide (LPS) on hippocampal corticosteroid receptors were studied in the rat. Type I (mineralocorticoid) and type II (glucocorticoid) receptors were measured in hippocampal cytosolic fractions with the radioligand binding technique, using <sup>3</sup>H-corticosterone and <sup>3</sup>H-RU 28362, respectively. LPS, administered intraperitoneally (50 µg/kg 8 h before sacrifice or 100 µg/kg injected twice, 16 and 8 h before sacrifice) to rats which had been previously adrenalectomized to allow for clearance of endogenous corticosterone, did not modify either type of corticosteroid receptors in the hippocampus. IL-1, IL-6, TNF or saline were injected intracerebroventricularly (50 ng/rat) and the animals were killed 3 h after. Type I receptors were not affected by any of the cytokines studied. Moreover, no changes in type II receptors were observed after IL-1 or IL-6 administration. In contrast, hippocampal type II receptors were dramatically decreased after the injection of TNF. The TNF-induced downregulation of type II receptors was secondary to a marked decrease in the affinity of the receptors (K<sub>d</sub> increased 7.2-fold), accompanied by a 51% decrease in receptor number (B<sub>max</sub>). These results emphasize the important role played by TNF in the modulation of the hypothalamic-pituitary-adrenal axis during immune/inflammatory processes and extend the central sites of action of this cytokine to the corticosteroid receptors of the hippocampus.

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          Author and article information

          S. Karger AG
          09 April 2008
          : 62
          : 1
          : 47-54
          Department of Psychobiology, Cajal Institute, CSIC, Madrid, Spain
          126987 Neuroendocrinology 1995;62:47–54
          © 1995 S. Karger AG, Basel

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          Page count
          Pages: 8
          Neuroimmune Interactions


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