Cytotoxic action of IL-1 beta against pancreatic islets is mediated via nitric oxide formation and is inhibited by NG-monomethyl-L-arginine

Abstract

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 NG-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.