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Interleukin-1ß Enhances Interleukin-1 Receptor Antagonist Content in Human Somatotroph Adenoma Cell Cultures¹

Max-Planck-Institute of Psychiatry, Department of Endocrinology, Munich, Germany (J.S., U.R., U.H., U.P., G.K.S.); Division of Endocrinology, Department of Medicine, University of Essen, Germany (J.S.); Laboratory Fisiología y Biología Molecular, Department of Biology, Facultad de Ciencas Exactas y Naturales University of Buenos Aires and Consejo Nacional de Investigaciones Cientifìcas y Técnicas, Buenos Aires, Argentina (E.A.); Department of Neurosurgery, Klinikum Mannheim, University of Heidelberg, Mannheim, Germany (M.L.); Department of Neurosurgery (A.M.) and Department of Medicine (C.J.S.), University of Munich, Germany

Address all correspondence and requests for reprints to: G. K. Stalla Max Planck Institute of Psychiatry, Department of Endocrinology, Kraepelinstrasse 10, D-80804 Munich, Germany. E-mail: stalla{at}mpipsykl.mpg.de

In addition to the well-known modulation of immune and inflammatory responses, 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 present study, we investigated the regulation of IL-1ra protein by IL-1ß (1–100 U/mL) in human somatotroph adenomas (n = 9) cultured for 12–48 h. IL-1ß significantly enhanced the concentration of IL-1ra dose dependently in the somatotroph adenoma cell lysates, whereas IL-1ra concentrations remained unchanged in the culture supernatants. Furthermore, basal IL-1ra concentrations were significantly higher in the cell lysates compared with the corresponding culture supernatants. The regulation of IL-1ra in somatotroph adenoma cells is different from human cultured monocytes, in which IL-1ß significantly stimulated IL-1ra secretion into the culture supernatants, and no change of intracellular IL-1ra content was observed. Incubation of the somatotroph adenoma cells with 100 U/mL IL-1ß did not result in a change of GH concentrations in the culture supernatants. Enhancement of intracellular IL-1ra protein by IL-1ß may represent a mechanism intrinsic to somatotroph adenoma cells to counterregulate the response to IL-1ß on hormone secretion or cellular growth.

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