ACUTE AND CHRONIC EFFECTS OF SYSTEMIC ADMINISTRATION OF INTERLEUKIN-1-BETA AND ENDOTOXIN ON THE HYPOTHALAMIC-PITUITARY-ADRENAL AXIS IN THE RAT

We evaluated the response of the hypothalamic-pituitary-adrenal (HPA) axis to the acute and chronic administration of interleukin-1 beta (IL -1 beta), and how these responses compared to those observed following the administration of the endotoxin lipopolysaccharide (LPS). The acu te administration of IL-1 beta decreased CRH content of the stalk medi an eminence and ACTH content of the pituitary. Both plasma ACTH and co rticosterone demonstrated a significant increase following acute IL-1 beta administration. Chronic IL-1 beta treatment decreased the body we ight of rats by 40%. Chronic treatment also significantly decreased th e crh content of the stalk median eminence by 50% while at the same ti me significantly increased pituitary ACTH content by 45%. Chronic LPS administration initially decreased body weight in a fashion similar to IL-1 beta treated animals. However, after 4 days LPS-treated rats dem onstrated normal weight gain. LPS did not affect CRH or ACTH concentra tions. This study shows that acute administration of IL-1 beta is a po tent activator of the HPA axis and that chronic administration of IL-1 beta results in an attenuation of this response. Chronic administrati on of LPS failed to reproduce the effects of IL-1 beta on the HPA axis suggesting that the immune response to LPS becomes desensitized much more rapidly than to IL-1 beta.