AbstractInterleukin‐1 (IL‐1) receptors with kinetics, pharmacological and biochemical characteristics of type I IL‐1 receptors have been identified in the mouse neuro‐endocrine‐immune axis. In the present study, we examined thein‐vitroandin‐vivomodulation of IL‐1 receptors by stress and endotoxin treatment. The treatment of AtT‐20 mouse pituitary adenoma cells for 24 hr with neuro‐endocrine mediators of stress such as corticotropin releasing factor (CRF) and catecholamine (β2adrenergic) receptor agonists produced a dose‐dependent increase in cAMP and [125I]IL‐1α binding. In contrast, somatostatin and dexamethasone significantly inhibited CRF‐stimulated cAMP production and decreased both basal and CRF‐mediated increase of [125I]IL‐1α binding. Furthermore, in keeping with the effects of stress mediators to upregulate IL‐1 receptors in AtT‐20 cells, ether‐laparotomy stress in mice resulted in a significant increase in [125I]IL‐1α binding in the pituitary with no significant alterations observed in the brain; in contrast, [125I]oCRF binding in the pituitary was significantly decreased after the ether‐laparotomy stress.Next, we investigated the modulation of IL‐1β levels and [125I]IL‐1α binding following endotoxin lipopolysaccharide (LPS) treatment. IL‐1β levels were dramatically increased in the peripheral tissues (pituitary, tests and spleen) at 2–6 hr after a single LPS injection (30 μg LPS/mouse) However, no significant changes were observed in brain (hippocampus and hypothalamus). [125I]IL‐1α binding in the pituitary gland, liver, spleen and testis was significantly decreased at 2 hr following a single administration of both low (30 μg LPS/mouse) and high (300 μg LPS/mouse) doses of endotoxin. [125I]IL‐1α binding in the hippocampus was not significantly altered at 2 hr by a low dose of LPS and was significantly decreased by high dose administration of LPS (300 μg/mouse). Following two LPS injections (at 0 and 12 hr), dramatic increases in IL‐1β concentrations in the hypothalamus, hippocampus, spleen and testis were observed at 2 hr after the second LPS injection; a small but statistically nonsignificant change was evident in the pituitary. Moreover, dramatic decreases in [125I]IL‐1α binding were seen after two injections of 30 μg LPS/mouse in both central and peripheral tissues. These data provide further support for a role for IL‐1 in co‐ordinating neuro‐endocrine‐immune responses to stress and infection.