Randomized safety studies of intravenous perflubron emulsion. II. Effects on immune function in healthy volunteers

Particle size distribution is a major determinant of particle clearance by the mononuclear phagocytic system and the potential for concomitant activat ion of resident macrophages. To test the safety of a second-generation perf lubron-based emulsion (60% perfluorocarbon [PFC] wt/vol; Oxygent(TM) [Allia nce Pharmaceutical Corp., San Diego, CA]) with a small mean particle size, two parallel, randomized, double-blinded, placebo-controlled studies were c onducted in 48 healthy volunteers (n = 24 per study). The study described h erein focuses on safety concerning immune function. The primary endpoint wa s defined prospectively as delayed hypersensitivity skin test responses wit h lymphocyte proliferative responses to mitogenic stimulation providing a s econdary measure for changes in cell-mediated immunity. Subjects received e ither perflubron emulsion IV (1.2 g PFC/kg or 1.8 g PFC/kg) or saline (3 mL /kg) control. Perflubron emulsion had no effect on delayed hypersensitivity skin reactions, lymphocyte proliferative potential, circulating immunoglob ulins, complement activation, or plasma levels of the inflammatory cytokine s, tumor necrosis factor-alpha, interleukin-1 alpha, and interleukin-1 beta . Perflubron emulsion was generally well tolerated, although there was a do se-dependent increase in minor flu-like symptoms in the perflubron treatmen t groups at 24 h after dosing. Increased serum levels of interleukin-6 were observed in those subjects exhibiting febrile responses. The clinical safe ty profile of perflubron emulsion supports its continued investigation as a temporary oxygen carrier in surgical patients to reduce exposure to alloge neic blood transfusion.