CYTOTOXIC ACTION OF IL-1-BETA AGAINST PANCREATIC-ISLETS IS MEDIATED VIA NITRIC-OXIDE FORMATION AND IS INHIBITED BY N(G)-MONOMETHYL-L-ARGININE

IL-1-beta has been previously shown to act as a cytotoxic agent in islets. Here we show by electron microscopy of alginate encapsulated islets, that islet cell lysis is induced by culturing islets for 24 or 48 h in the presence of IL-1-beta. The extent of lysis depends on the IL-1-beta concentration and is slightly enhanced by the addition of TNF-alpha. Cells can be protected from lysis by N(G)-monomethyl-L-arginine. Lysis is paralleled by an increase in nitrite concentration in culture supernatants of whole islets but not in supernatants of isolated endocrine cells. The results indicate that IL-1-beta toxicity occurs via inducing in non-endocrine islet cells the synthesis and release of nitric oxide, which has been shown earlier to be highly toxic for islet cells.