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Lung-protective effects of the metalloporphyrinic peroxynitrite decomposition catalyst WW-85 in interleukin-2 induced toxicity |
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| Authors: | Maybauer Dirk M Maybauer Marc O Szabó Csaba Westphal Martin Traber Lillian D Enkhbaatar Perenlei Murthy Kanneganti G K Nakano Yoshimitsu Salzman Andrew L Herndon David N Traber Daniel L |
| Institution: | a 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 b Department of Surgery, Investigational Intensive Care Unit, The University of Texas Medical Branch and Shriners Burns Hospital for Children at Galveston, TX, USA c Department of Anesthesiology and Intensive Care, University of Muenster, Muenster, Germany d Inotek Pharmaceuticals Corporation, Beverly, MA, USA |
| Abstract: | 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. |
| Keywords: | Cancer therapy Lung lymph flow Nitric-oxide Transvascular fluid flux Vascular leakage |
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