INTERLEUKIN-1-BETA ENHANCES INTERLEUKIN-1 RECEPTOR ANTAGONIST CONTENTIN HUMAN SOMATOTROPH ADENOMA CELL-CULTURES

In addition to the well-known modulation of immune and inflammatory re sponses, the interleukin-1 (IL-1) system has been shown to be involved in the regulation of anterior pituitary hormone secretion and growth. We previously demonstrated that IL-1 receptor antagonist (IL-1ra) is expressed in human pituitary adenomas cultured in vitro. In the presen t study, we investigated the regulation of IL-1ra protein by IL-1 beta (1-100 U/mL) in human somatotroph adenomas (n = 9) cultured for 12-48 h. IL-1 beta significantly enhanced the concentration of IL-1ra dose dependently in the somatotroph adenoma cell lysates, whereas IL-1ra co ncentrations remained unchanged in the culture supernatants. Furthermo re, basal IL-1ra concentrations were significantly higher in the cell lysates compared with the corresponding culture supernatants. The regu lation of IL-1ra in somatotroph adenoma cells is different from human cultured monocytes, in which IL-1 beta significantly stimulated IL-1ra secretion into the culture supernatants, and no change of intracellul ar IL-1ra content was observed. Incubation of the somatotroph adenoma cells with 100 U/mL IL-1 beta did not result in a change of GK concent rations in the culture supernatants. Enhancement of intracellular IL-1 ra protein by IL-1 beta may represent a mechanism intrinsic to somatot roph adenoma cells to counterregulate the response to IL-1 beta on hor mone secretion or cellular growth.