Lung-protective effects of the metalloporphyrinic peroxynitrite decomposition catalyst WW-85 in interleukin-2 induced toxicity.

Dirk M Maybauer, Marc O Maybauer, Csaba Szabó, Martin Westphal, Lillian D Traber, Perenlei Enkhbaatar, Kanneganti G K Murthy, Yoshimitsu Nakano, Andrew L Salzman, David N Herndon, Daniel L Traber

Department of Anesthesiology, Investigational Intensive Care Unit, The University of Texas Medical Branch and Shriners Burns Hospital for Children at Galveston, 301 University Blvd., Galveston, TX 77555-0833, USA.

Biochemical and biophysical research communications 2008 Dec 19

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Recombinant interleukin-2 (IL-2) therapy for malignancy is associated with a pulmonary vascular leakage syndrome (VLS) similar to that seen in sepsis. We investigated the possibility that the IL-2-induced VLS may be associated with the release of peroxynitrite (ONOO(-)), and used a model of IL-2-induced VLS in sheep to test the effects of the ONOO(-) decomposition catalyst WW-85. Eighteen sheep were chronically instrumented and randomly divided into three groups (n=6 per group): sham: lactated Ringer's solution, control: IL-2, and treatment: IL-2 and WW-85. Treatment with WW-85 significantly improved lung transvascular fluid flux, decreased lipid peroxidation, limited iNOS as well as PAR intensity, prevented tachycardia, and attenuated the increase in core body temperature resulting from IL-2 treatment. These findings suggest that ONOO(-) plays a pivotal role in the pathology of IL-2-induced pulmonary VLS, and that WW-85 may become a useful treatment option.

Citation

Dirk M Maybauer, Marc O Maybauer, Csaba Szabó, Martin Westphal, Lillian D Traber, Perenlei Enkhbaatar, Kanneganti G K Murthy, Yoshimitsu Nakano, Andrew L Salzman, David N Herndon, Daniel L Traber. Lung-protective effects of the metalloporphyrinic peroxynitrite decomposition catalyst WW-85 in interleukin-2 induced toxicity. Biochemical and biophysical research communications. 2008 Dec 19;377(3):786-91