MECHANISMS OF ACTIVATION OF THE PITUITARY-ADRENAL AXIS BY TISSUE-INJURY IN THE RAT

To characterize the mechanisms of the pituitary-adrenal (P-A) response to tissue injury, rats were injected intramuscularly (IM) with turpen tine. This resulted in marked elevations in the plasma concentrations of ACTH and corticosterone within the first hour after injection, whic h were attenuated by either total deafferentation of the medial basal hypothalamus (MBH) or neonatal capsaicin pretreatment. The plasma conc entrations of corticosterone remained elevated for 18 h in turpentine- injected rats, despite a return of ACTH toward control values (by 2-4 h). Bioactive concentrations of interleukin-6 (IL-6) in plasma rose ma rkedly after turpentine, and its concentrations were significantly cor related with plasma corticosterone concentrations 4-8 h after turpenti ne. Pretreatment with IL-1 receptor antagonist (IL-1ra) attenuated the release of IL-6 and had a marginal effect on the corticosterone respo nse 6 h after turpentine: These results suggest that the early and lat e phase of the P-A response to tissue injury are mediated by different mechanisms.