CYTOKINE REGULATION OF CORTICOSTEROID RECEPTORS IN THE RAT HIPPOCAMPUS - EFFECTS OF INTERLEUKIN-1, INTERLEUKIN-6, TUMOR-NECROSIS-FACTOR ANDLIPOPOLYSACCHARIDE

The effects of interleukin-1 beta(IL-1), interleukin-6(IL-6), tumor ne crosis factor alpha(TNF) and lipopolysaccharide (LPS) on hippocampal c orticosteroid receptors were studied in the rat. Type I (mineralocorti coid) and type II (glucocorticoid) receptors were measured in hippocam pal cytosolic fractions with the radioligand binding technique, using H-3-corticosterone and H-3-RU 28362, respectively. LPS, administered i ntraperitoneally (50 mu g/kg 8 h before sacrifice or 100 mu g/kg injec ted twice, 16 and 8 h before sacrifice) to rats which had been previou sly adrenalectomized to allow for clearance of endogenous corticostero ne, did not modify either type of corticosteroid receptors in the hipp ocampus. IL-1, IL-6, TNF or saline were injected intracerebroventricul arly (50 ng/rat) and the animals were killed 3 h after. Type I recepto rs were not affected by any of the cytokines studied. Moreover, no cha nges in type II receptors were observed after IL-1 or IL-6 administrat ion. In contrast, hippocampal type II receptors were dramatically decr eased after the injection of TNF. The TNF-induced downregulation of ty pe II receptors was secondary to a marked decrease in the affinity of the receptors (K-d increased 7.2-fold), accompanied by a 51% decrease in receptor number (B-max). 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 site s of action of the cytokine to the corticosteroid receptors of the hip pocampus.