¹Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

²Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

Correspondence to: P Robbins, Department of Molecular Genetics and Biochemistry, W1246 BST, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261 USA

Interleukin-1 is a potent pro-inflammatory cytokine that has been shown to inhibit islet cell function as well as to activate Fas-mediated apoptosis in a nitric oxide-dependent manner. Furthermore, this cytokine is effective in recruiting lymphocytes that mediate cell destruction in IDDM onset. The insulin-like growth factor I (IGF-I) has been shown to block IL-1 actions in vitro. We hypothesized that gene transfer of the insulin-like growth factor I to intact human islets could prevent IL-1-induced cell dysfunction and sensitization to Fas-triggered apoptosis activation. Intact human islets were infected with adenoviral vectors encoding IGF-I as well as -galactosidase and enhanced green fluorescent protein as controls. Adenoviral gene transfer of human IGF-I prevented IL-1-mediated nitric oxide production from human islets in vitro as well as the suppression of cell function as determined by glucose-stimulated insulin production. Moreover, IGF-I gene transfer prevented IL-1-induced, Fas-mediated apoptosis. These results suggest that locally produced IGF-I from cultured islets may be beneficial in maintaining cell function and promoting islet survival before and following islet transplantation as a potential therapy for type I diabetes. Gene Therapy (2000) 7, 2015-2022.

gene therapy; IL-1; IGF-I; islets; adenovirus