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 med iators involved in the modulation of the neuroimmunoendocrine response to stress. IL-1 is a potent activator of the hypothalamic-pituitary-a drenal (HPA) axis in rodents. In the immune system, glucocorticoids mo dulate 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 s ystem. To this purpose, we carried out a series of studies to investig ate the effects of various manipulations of the HPA axis on IL-1 bindi ng to the murine hippocampus. Our results show that IL-1 receptor leve ls 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. Cortico sterone (CORT) resulted in a small reduction in IL-1 receptors only wh en injected subchronically at the dose of 5 mg/kg. When it was given a t a lower dose (1.25 mg/kg), injected chronically or implanted subcuta neously as CORT pellets for 8 days, no effect was observed. Neither gl ucocorticoid modified IL-1 binding when administered as a single injec tion. Saturation studies after subchronic corticosteroid treatment did not reveal modifications in the number and/or affinity of IL-1 recept ors in the hippocampus. The regulation of IL-1 receptors by glucocorti coids was also studied following stimulation of IL-1 production by lip opolysaccharide (LPS). LPS administration (30 mu g i.p. 24 and 12 h be fore sacrifice) resulted in a significant reduction in IL-1 binding, b ut this effect was not modified by DEX treatment. Exposure to stress ( sound, cold exposure or foot shock) once a day for 5 days did not modi fy IL-1-binding levels in the hippocampus. Moreover, hippocampal IL-1 receptor binding was not changed 2 or 7 days after adrenalectomy. The results of the present study suggest that, in contrast to what has bee n observed in the immune system, IL-1 receptor levels in the murine hi ppocampus are relatively resistant to modulation by varying levels of circulating glucocorticoids.