CYTOKINES AND THE BRAIN CORTICOSTEROID RECEPTOR BALANCE - RELEVANCE TO PATHOPHYSIOLOGY OF NEUROENDOCRINE-IMMUNE COMMUNICATION

Interleukin-l (IL-1) and interleukin-6 (IL-6), and their cognate recep tors, are expressed in hippocampal neurons, which are targets for cort icosteroid hormones. Corticosteroids bind to intracellular receptors, that is, mineralocorticoid (MRs) and glucocorticoid receptors (GRs). M Rs respond to low concentrations of the steroid, while higher concentr ations are needed for additional activation of GRs. MR occupation appe ars relevant in hippocampal neurons for stability of ongoing transmiss ion, for basal activity and sensitivity of the stress response system, and for behavioural reactivity and response selection. Additional tra nsient GR activation suppresses excitability, facilitates recovery fro m the stress response, and promotes information storage. Thus, the bal ance of MR- and GR-mediated effects appears critical for the long-term control exerted by corticosteroids over specific aspects of neuronal activity, stress responsiveness, and behavioural adaptation. Administr ation of IL-1 produces a long-lasting increase in corticosterone. IL-I also influences MR function in hippocampus and causes a shift in the MR/GR balance, which may underlie prolonged activation of the HPA axis during an immune response.