Human somatotrophic (GH) adenoma cells interleukin (IL)-1β induces production of il-6 and il-8.
Signe Diness1, Æse Krogh Rasmussen1, Klaus Bendtzen2, Michael Kosteljanetz3 & Ulla Feldt-Rasmussen1
Aim: to establish a human in vitro system for the study of pituitary cells in culture and subsequently to study the influence of the pro-inflammatory cytokines interleukin (IL)-1β and tumour necrosis factor (TNF)-α on the function of the somatotrophic cells inclusive the ability of the cells to produce IL-6 and IL-8.
Methods: Pituitary adenomas were obtained from hypophysectomies of patients with acromegaly. The tissue was enzymatically digested and cultured in 24-chamber polystyrene plates in medium supplemented with nutritional factors and antibiotics and with 105 cells per well. GH and cytokines were measured in the harvested supernatants.
Results: GHRH (GH releasing hormone) (30,000 ng/ml) stimulated significantly 72 h GH production from the somatotrophic cells (25% (1050), median (range), n=12 chambers, P<0.05) compared to controls (3525 mU/l (49-17450)), while somatostatin (0.110,000 ng/ml) inhibited the 72 h GH production from the cells compared to controls (P<0.05, n=1218). The GH production was significantly lower in cells cultured more than 15 days compared to younger cell cultures (<15 days). IL-1β (1000 and 100 pg/ml) stimulated modestly the 72 h GH production from the cells compared to controls (20% (1050), n=18) and (15% (1060), n=18), while TNF-α had no influence the function of the cells. The effect of IL-1β was reversible. IL-1β (10,000, 100, 10 pg/ml) also stimulated 72 h IL-6 and IL-8 production from the cells. IL-1β (10,000 pg/ml) induced a mean 12.3 and 8.2-fold increase in IL-6 and IL-8, respectively compared to control (mean 1472 pg/ml and 1948 pg/ml, respectively) in 4 different cultures.
Conclusion: We have established a robust in vitro system for studying the function of GH producing pituitary cells; GH production from the cells exhibited the expected responses to GHRH and somatostatin. IL-1β further stimulated the release of IL-6 and IL-8 from the cells, an effect that has been established also in other endocrine cells such as e.g. thyrocytes. The physiological and/or pathophysiological roles of these findings remain to be shown.