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Induction of Apoptosis by the Hydrocarbon Oil Pristane: Implications for Pristane-Induced Lupus¹

Nicola Calvani^*, Roberto Caricchio, Marco Tucci^*, Eric S. Sobel, Franco Silvestris^*, Paola Tartaglia^* and Hanno B. Richards^2,

^* Department of Internal Medicine and Clinical Oncology, University of Bari, Bari, Italy; Department of Medicine, Division of Rheumatology, University of Pennsylvania, Philadelphia, PA 19104; and Department of Medicine, Division of Rheumatology and Clinical Immunology, University of Florida, Gainesville, FL 32610

Intraperitoneal injection of the hydrocarbon oil pristane into normal mice leads to a lupus-like autoimmune syndrome. Although advances in defining the roles of cellular and humoral mediators involved in this syndrome have been made, the mechanisms that initiate a break in tolerance leading to autoimmunity remain unknown. We describe in this study that pristane induces apoptosis both in vivo and in vitro. Pristane arrests cell growth and induces cell death by apoptosis via the mitochondrial pathway of caspase activation in a dose-dependent manner. Nuclear autoantigens created by pristane-induced apoptosis of lymphoid cells within the peritoneal cavity in the setting of a profoundly altered cytokine milieu may be the initiating event in the development of autoimmunity in this syndrome. These findings suggest that apoptosis may be a critical initial event in the pathogenesis of pristane-induced lupus and are of potential relevance for human systemic lupus erythematosus.

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