INVOLVEMENT OF INTERLEUKIN-1 AND INTERLEUKIN-1 RECEPTOR ANTAGONIST INRAT PITUITARY CELL-GROWTH REGULATION

Interleukin-1 (IL-1), one of the mediators of the interaction between the immune and the neuroendocrine system, is well known to modulate an terior pituitary hormone secretion. As IL-1 influences growth of vario us cell types, we investigated whether IL-1 is also a growth factor of pituitary cells. We demonstrate that IL-1 dose and time dependently i nhibits the growth of normal rat pituitary cells under serum-free cond itions. The inhibitory potencies of IL-1 alpha (ED(50), 8 pg/ml) and I L-1 beta (ED(50), 6 pg/ml) were nearly identical. In the presence of l ow amounts of serum, both IL-1 alpha (ED(50), 130 pg/ml) and IL-1 beta (ED(50), 90 pg/ml) were less effective in inhibiting growth. The IL-1 -induced growth inhibition was IL-1 receptor mediated, because both IL -1 alpha- and IL-1 beta-mediated growth suppression could be completel y reversed by the IL-1 receptor antagonist, the physiological counterp art of IL-1. In the mammosomatotroph GH, rat pituitary tumor cell line , IL-1 failed to influence growth, indicating that either IL-1 recepto rs are missing or the IL-1 signaling pathway is uncoupled from the gro wth regulation. In contrast to growth, in our rat pituitary monolayer cell culture system, IL-1 did not affect ACTH, GH, or PRL secretion as described previously. This discrepancy suggests the involvement of di fferent mechanisms in the IL-1-induced mediation of growth and hormone secretion.