Effects of recombinant human interleukin-1 alpha, -1 beta, 2 and 6 on ACTH synthesis and release in the mouse pituitary tumour cell line AtT-20

Abstract

The effects of recombinant human interleukin (rhIL)-1 alpha, -1 beta, 2 and 6 on the release of ACTH from the ACTH-producing tumour cell line AtT-20 of the mouse were studied during relatively long periods of incubation. Levels of ACTH in the media, measured by radioimmunoassay, were increased by the addition of rhIL-1 alpha or -1 beta after latent periods of more than 4 h. RhIL-1 alpha and -1 beta were almost equally potent in this experiment and the minimum, half-maximum and maximum effective concentrations of both rhIL-1 alpha and -1 beta were about 0.1 pmol/l, 1-3 pmol/l and 10-100 pmol/l respectively. During incubation with rhIL-1 beta, immunoreactive ACTH levels and mRNA levels of the ACTH precursor pro-opiomelanocortin in cells also increased without apparent changes in the growth rate of the cells. Although the AtT-20 cells used in this study were quite insensitive to human/rat corticotrophin-releasing hormone (CRH), the cells showed a significant response to CRH after incubation with rhIL-1 beta. RhIL-6 showed similar effects to those of rhIL-1 beta on ACTH synthesis and release; increasing ACTH in cells and media after a certain latent period. On the other hand, rhIL-2 did not change ACTH levels in the AtT-20 cells in this study. These observations indicate that rhIL-1 alpha, -1 beta and rhIL-6 have direct effects on ACTH-producing cells to stimulate the release and synthesis of ACTH after a latent period.