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 immune system. IL-1 is present and formed locally in the brain as demonstrated by biochemical and immunocytochemical methods. Various immunomodulatory and neuroendocrine effects of IL-1 have been reported, including induction of several morphological changes in the endocrine cells of experimental animals and humans. IL-1 is present in two molecular forms (IL-1 alpha and IL-1 beta) that activate specific receptors for IL-1. In the present study we investigated the possible effect of recombinant human IL-1 alpha and IL-1 beta and recently cloned anti-human IL-1 receptor antibody (M10) on cell proliferation in the anterior and the intermediate lobe of the pituitary gland of the rat. In vivo labelling with bromodeoxyuridine (BrdU) and immunocytochemical staining with 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 micrograms/kg body weight) incorporation of BrdU into pituitary intermediate 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 proliferation was receptor specific, since stimulation was blocked by anti-IL-1 receptor antibody. On the other hand, recombinant human IL-1 alpha did not affect BrdU incorporation and the proliferation of pituitary pars intermedia cells.(ABSTRACT TRUNCATED AT 250 WORDS)