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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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

Fingerprint

Peroxynitrous Acid
Interleukin-2
Toxicity
Decomposition
Lung
Catalysts
Blood Vessels
Sheep
Therapeutics
Pathology
Body Temperature
Tachycardia
Lipid Peroxidation
Sepsis
Fluxes
Lipids
Fluids

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

Lung-protective effects of the metalloporphyrinic peroxynitrite decomposition catalyst WW-85 in interleukin-2 induced toxicity. / Maybauer, Dirk M.; Maybauer, Marc O.; Szabo, Csaba; Westphal, Martin; Traber, Lillian D.; Enkhbaatar, Perenlei; Murthy, Kanneganti G K; Nakano, Yoshimitsu; Salzman, Andrew L.; Herndon, David; Traber, Daniel L.

In: Biochemical and Biophysical Research Communications, Vol. 377, No. 3, 19.12.2008, p. 786-791.

Research output: Contribution to journalArticle

Maybauer, Dirk M. ; Maybauer, Marc O. ; Szabo, Csaba ; Westphal, Martin ; Traber, Lillian D. ; Enkhbaatar, Perenlei ; Murthy, Kanneganti G K ; Nakano, Yoshimitsu ; Salzman, Andrew L. ; Herndon, David ; Traber, Daniel L. / Lung-protective effects of the metalloporphyrinic peroxynitrite decomposition catalyst WW-85 in interleukin-2 induced toxicity. In: Biochemical and Biophysical Research Communications. 2008 ; Vol. 377, No. 3. pp. 786-791.
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