Corticosteroid regulation of IL-1 receptors in the mouse hippocampus: effects of glucocorticoid treatment, stress, and adrenalectomy.
Interleukin-1 (IL-1) and glucocorticoid hormones represent two key mediators involved in the modulation of the neuroimmunoendocrine response to stress. IL-1 is a potent activator of the hypothalamic-pituitary-adrenal (HPA) axis in rodents. In the immune system, glucocorticoids modulate IL-1 production and a number of IL-1 receptors. However, little information is currently available about the modulatory effects that glucocorticoids might exert on IL-1 receptors in the central nervous system. To this purpose, we carried out a series of studies to investigate the effects of various manipulations of the HPA axis on IL-1 binding to the murine hippocampus. Our results show that IL-1 receptor levels in the hippocampus were slightly decreased below control values in dexamethasone (DEX)-treated animals (0.25 or 1 mg/kg i.p. every 12 h) either in subchronic (5 doses) or chronic (8 days) treatments. Corticosterone (CORT) resulted in a small reduction in IL-1 receptors only when injected subchronically at the dose of 5 mg/kg. When it was given at a lower dose (1.25 mg/kg), injected chronically or implanted subcutaneously as CORT pellets for 8 days, no effect was observed. Neither glucocorticoid modified IL-1 binding when administered as a single injection. Saturation studies after subchronic corticosteroid treatment did not reveal modifications in the number and/or affinity of IL-1 receptors in the hippocampus. The regulation of IL-1 receptors by glucocorticoids was also studied following stimulation of IL-1 production by lipopolysaccharide (LPS).(ABSTRACT TRUNCATED AT 250 WORDS)
Betancur
C
C
Department of Psychobiology, Cajal Institute, CSIC, Madrid, Spain.
Lledo
A
A
Borrell
J
J
Guaza
C
C
D000315:Adrenalectomy; D000818:Animals; D003345:Corticosterone / Q000008:administration & dosage / Q000494:pharmacology; D003907:Dexamethasone / Q000008:administration & dosage / Q000494:pharmacology; D005938:Glucocorticoids / Q000494:pharmacology*; D006624:Hippocampus / Q000378:metabolism*; D007375:Interleukin-1 / Q000096:biosynthesis / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D017472:Receptors, Interleukin-1 / Q000187:drug effects / Q000378:metabolism*; D013312:Stress, Physiological / Q000378:metabolism*
D005938:Glucocorticoids; D007375:Interleukin-1; D008070:Lipopolysaccharides; D017472:Receptors, Interleukin-1; D003907:Dexamethasone; D003345:Corticosterone