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

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

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17 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)786-791
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume377
Issue number3
DOIs
StatePublished - Dec 19 2008

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Keywords

  • Cancer therapy
  • Lung lymph flow
  • Nitric-oxide
  • Transvascular fluid flux
  • Vascular leakage

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Cell Biology
  • Molecular Biology

Cite this

Maybauer, D. M., Maybauer, M. O., Szabo, C., Westphal, M., Traber, L. D., Enkhbaatar, P., Murthy, K. G. K., Nakano, Y., Salzman, A. L., Herndon, D., & Traber, D. L. (2008). Lung-protective effects of the metalloporphyrinic peroxynitrite decomposition catalyst WW-85 in interleukin-2 induced toxicity. Biochemical and Biophysical Research Communications, 377(3), 786-791. https://doi.org/10.1016/j.bbrc.2008.10.066