An inhibitory effects of interleukin-1a on basal gonadotropin release in the ovariectomized rhesus monkey: reversal by a corticotropin-releasing factor antagonist

Abstract

Interleukin-1 (IL-1), an important component of the immune system, has recently been shown to influence the release of several hormones in the rodent. In this paper, the effectiveness of IL-1a in modulating basal gonadotropin secretion as well as cortisol release in the primate has been investigated. Eight adult ovariectomized rhesus monkeys were given a 30-min intracerebroventricular infusion of physiological saline (n = 5), various doses of IL-1a (17 micrograms n = 5; 8.5 micrograms; n = 3; 4.2 micrograms n = 5; and 2.1 micrograms n = 4) or IL-1a plus a CRF antagonist (n = 5). LH and FSH concentrations were measured at 15-min intervals during the 3-h preinfusion baseline control and the 5-h postinfusion period, while cortisol concentrations were determined at 45-min intervals. While LH concentrations remained unchanged in the monkeys receiving saline only, they decreased significantly after the 30-min IL-1a infusion. By hour 5 after IL-1a administration, mean (+/- SE) hourly areas under the LH curves (expressed as a percentage of preinfusion baseline) were 27.7% +/- 7.3 (17 micrograms IL-1a), 31.9% +/- 8.4 (8.5 micrograms), 33.3% +/- 5.5 (4.2 micrograms), and 39% +/- 4.0 (2.1 micrograms) (P less than 0.05 vs. morning control). FSH concentrations were also significantly decreased after IL-1a, 17 micrograms: by hour 5, they were 67.4% +/- 5.0 of baseline control. While cortisol concentrations decreased thoughout the experiment in the animals receiving saline, they increased with all IL-1a doses: overall mean (+/- SE) postinfusion concentrations were 21.8 +/- 1.1 (saline), 49.5 +/- 2.2 (IL-1a, 17 micrograms), 35.1 +/- 1.9 (8.5 micrograms), 45.7 +/- 1.5 (4.2 micrograms), and 39.5 +/- 1.5 (2.1 micrograms) micrograms/dl (P less than 0.05 IL-1a vs. saline). Concomitant infusion of the CRF antagonist, [D-Phe12, NLE 21,38caMe LEU37] CRF (12-41), (120-360 micrograms), prevented the IL-1a induced LH inhibition. By hour 5, areas under LH curves were 33.5% +/- 1.7 for IL-1a alone and 99.2% +/- 4.2 (NS vs. saline) for IL-1a + CRF antagonist. The CRF antagonist also blocked the ability of IL-1a to increase cortisol secretion: mean cortisol concentrations were 28.6 +/- 1.4 micrograms/dl (NS vs. saline). The results clearly indicate that the cytokine IL-1a inhibits pulsatile LH and FSH secretion in the ovariectomized rhesus monkey and demonstrate that this inhibition is causally related to the activation of CRF by this cytokine.(ABSTRACT TRUNCATED AT 400 WORDS)