CABERGOLINE EFFECT ON SECRETION OF sICAM-1 AND CYTOKINES IN HUMAN PITUITARY ADENOMA CELL CULTURE.

Our aim was to explore the interactions of intercellular adhesion molecule (sICAM-1), TNF-α (tumor necrosis factor-α), interleukin-1α (IL-1α) and interleukin-6 (IL-6) with dopamine agonists in a culture of adenomatous cells from an nonfunctional macroadenoma. Materials and methods. Tissue specimen from pituitary macroadenoma removed in transsphenoidal surgery was prepared for primary culture. Cells were counted and plated at 105/well into 24-well plates in a final volume of 1ml. Cabergoline in molar doses of 10-6, 10-7, 10-8, 10-9 was added and the cells were incubated for 4 days. sICAM-1, TNF-α, IL-1 α, IL-6 were measured from cell-culture supernatants by ELISA kits. Results. sICAM-1, TNF-α, IL-1α and IL-6 were detected in the untreated control cultures after a 4d period. There was a negative correlation between TNFα and IL-1α (p=0.007). The levels of PRL and hGH had measurable values above those found in culture medium without tumor cells. PRL positively correlated with IL-1α ( p=0.05). hGH positively correlated with cell proliferation (p=0.049). Cabergoline treatment showed that IL-6 progressively decreased with the dose, ranging from -27.41% to -76.44%. TNF-α significantly decreased (-65.90%; p<0.03) at the cabergoline 10-7 M dose. IL-1α progressively increased with cabergoline dose, ranging from -2.53% to 345 %. sICAM-1 was significantly reduced by cabergoline at 10-9 (-47.12 %; p= 0.045) and 10-6 M (-59.16%; p=0.01) doses. TNF-α positively correlated with PRL (p=0.025); IL-6 positively correlated with hGH (p=0.044); sICAM-1 negatively correlated with hGH (p=0.009), TNFα (p=0.025) and IL-1α (p=0.044). Conclusions. These data support the existence of an immunoendocrine network in pituitary tumorigenesis; TNF-α, IL-6, IL-1α, sICAM-1 significantly interfered by cabergoline treatment in a dose-dependent way. However, future studies on different types of pituitary tumours are needed to confirm these findings. [ABSTRACT FROM AUTHOR]