[The corticotropic axis response after subcutaneous endotoxin injection is not associated with the increase of plasma...

When injected through an intra-arterial (i. a.) cannula, LPS induced a rapid (15-30 min) and long-lasting (> 300 min) increase in plasma ACTH and corticosterone (CORT) levels. The duration of these responses depended on the LPS dose, and except for very small LPS doses, their amplitudes appeared independent of the dose of endotoxin. ACTH peaks (2,200 pg.ml-1) occurred between 30 and 120 min, whereas CORT always reached maximal levels at 120 min. Plasma Interleukin-1 beta (IL-1 beta) levels were always undetectable during the early phase of corticotropic stimulation, but increased strikingly 120 min after LPS injection. Increasing LPS doses, resulted in enhanced and prolonged IL-1 beta plasma circulating levels (up to 3.0 +/- 0.2 ng.ml-1). By contrast, no sub-cutaneous LPS dose used induced early increases in ACTH and CORT levels, whereas time-course of the hormonal response was evocative of the sustained phase of the corticotropic response to i. a. LPS, with both peaks occurring 120 min post-LPS. Increasing the s. c. LPS bolus 50-fold vs the i. a. dose did not affect the maximal amplitude of the ACTH response, whereas the amplitude of the CORT response, instead, appeared dependent on the LPS dose. On the other hand, even for the largest LPS doses, plasma IL-1 beta levels remained undetectable. Sub-cutaneous injection of LPS therefore appears as a new model for the study of the mechanisms of corticotropic responses to endotoxin without a direct involvement of bloodborne IL-1 beta.