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

Research output: Contribution to journalArticlepeer-review

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

Keywords

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

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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