A Central Mechanism Is Involved in the Secretion of ACTH in Response to IL-6 in Rats: Comparison to and Interaction with IL-1β

Publisher Website
Google Scholar
Abstract
The cytokines interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α are known to be potent effectors of ACTH secretion. Some of the peripheral effects of IL-1β appear to be related to the secretion of IL-6 induced by IL-1β. Thus, we evaluated the effect of IL-6 on ACTH secretion and its interaction with IL-1β. Rats received recombinant human (rhIL-6) or murine (rmIL-6) IL-6 through indwelling jugular cannulae. rhIL-6 (200 ng or 2 µg/rat) produced peak plasma ACTH levels which were 3- to 4-fold greater than basal levels. rmIL-6 produced similar responses. Neither species of IL-6 affected plasma prolactin levels. Comparison of rhIL-1β (200 ng) to rhIL-6 (200, 100 or 50 ng) showed that IL-6 elevated ACTH in a dose-dependent manner and that IL-1β was significantly more effective. IL-1β was also administered concomitantly with or 10 min after IL-6. Delivered together, IL-1lβ (100, 30 or 10 ng) and IL-6 (100 ng) produced significantly higher ACTH levels than when given alone. This additivity was also evident when IL-6 was given 10 min prior to IL-1β. The coadministration of IL-6 (2 µg) with corticotropin-releasing factor (CRF, 1 µg/kg, b.w.) also had an additive effect on ACTH secretion (at 20 min: 300 ± 40 pg/ml for CRF; 320 ± 83 pg/ml for IL-6; and 540 ± 44 pg/ml for CRF+ IL-6), whereas a higher dose of CRF (10 µg/kg b.w.) yielded ACTH levels of 1,000 ± 107 pg/ml at 20 min, with no further enhancement by IL-6. Incubation of pituitary cells with IL-6 alone (0.1, 1.0 or 3.0 nM) produced a slight but significant stimulation of ACTH secretion within 2 h in response to the higher doses of IL-6 only (p

This publication has 0 references indexed in Scilit: