INTERLEUKIN-1-BETA STIMULATES CELL-PROLIFERATION IN THE INTERMEDIATE LOBE OF THE RAT PITUITARY-GLAND

Interleukin-1 (IL-1) is a multifunctional monokine which possesses an impressive array of diverse actions relating to the function of the im mune system. IL-1 is present and formed locally in the brain as demons trated by biochemical and immunocytochemical methods. Various immunomo dulatory and neuroendocrine effects of IL-1 have been reported, includ ing induction of several morphological changes in the endocrine cells of experimental animals and humans. IL-1 is present in two molecular f orms (IL-1 alpha and IL-1 beta) that activate specific receptors for I L-1. In the present study we investigated the possible effect of recom binant human IL-1 alpha and IL-1 beta and recently cloned anti-human I L-1 receptor antibody (M10) on cell proliferation in the anterior and the intermediate lobe of the pituitary gland of the rat. In vivo label ling with bromodeoxyuridine (BrdU) and immunocytochemical staining wit h anti-BrdU monoclonal antibody were used as a sensitive index of cell proliferation. IL-1 beta was found to stimulate dose-dependently (0.1 -10 mu g/kg body weight) incorporation ofBrdU into pituitary intermedi ate cell nuclei, and positive correlation between the tested doses of IL-1 beta and BrdU-labelling index was noted (r=0.89; P<0.01). This IL -1 beta-induced stimulation of pituitary pars intermedia cell prolifer ation was receptor specific, since stimulation was blocked by anti-IL- 1 receptor antibody. On the other hand, recombinant human IL-1 alpha d id not affect BrdU incorporation and the proliferation of pituitary pa rs intermedia cells. In addition, neither of the cytokines tested in t he same experimental conditions showed any effect on the cell growth o f the pituitary pars anterior. These results suggest that IL-1 beta ma y be involved in the regulation of the cell growth of the pituitary in termediate lobe in rats.