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

doi:10.1016/j.bbrc.2008.10.066

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

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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 language	English (US)
Pages (from-to)	786-791
Number of pages	6
Journal	Biochemical and Biophysical Research Communications
Volume	377
Issue number	3
DOIs	https://doi.org/10.1016/j.bbrc.2008.10.066
State	Published - 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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Maybauer, D. M., Maybauer, M. O., Szabó, C., Westphal, M., Traber, L. D., Enkhbaatar, P., Murthy, K. G. K., Nakano, Y., Salzman, A. L., Herndon, D. N., & 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

Maybauer, DM, Maybauer, MO, Szabó, C, Westphal, M, Traber, LD, Enkhbaatar, P, Murthy, KGK, Nakano, Y, Salzman, AL, Herndon, DN & Traber, DL 2008, 'Lung-protective effects of the metalloporphyrinic peroxynitrite decomposition catalyst WW-85 in interleukin-2 induced toxicity', Biochemical and Biophysical Research Communications, vol. 377, no. 3, pp. 786-791. https://doi.org/10.1016/j.bbrc.2008.10.066

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

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",

author = "Maybauer, {Dirk M.} and Maybauer, {Marc O.} and Csaba Szab{\'o} and Martin Westphal and Traber, {Lillian D.} and Perenlei Enkhbaatar and Murthy, {Kanneganti G.K.} and Yoshimitsu Nakano and Salzman, {Andrew L.} and Herndon, {David N.} and Traber, {Daniel L.}",

note = "Funding Information: This work was supported in part by Grant GM066312 from the National Institutes of Health, by Grants 8820 and 8450 from the Shriners of North America, and the Inotek Pharmaceuticals Corporation, Beverly, MA, USA.",

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doi = "10.1016/j.bbrc.2008.10.066",

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AU - Maybauer, Dirk M.

AU - Maybauer, Marc O.

AU - Szabó, Csaba

AU - Westphal, Martin

AU - Traber, Lillian D.

AU - Enkhbaatar, Perenlei

AU - Murthy, Kanneganti G.K.

AU - Nakano, Yoshimitsu

AU - Salzman, Andrew L.

AU - Herndon, David N.

AU - Traber, Daniel L.

N1 - Funding Information: This work was supported in part by Grant GM066312 from the National Institutes of Health, by Grants 8820 and 8450 from the Shriners of North America, and the Inotek Pharmaceuticals Corporation, Beverly, MA, USA.

PY - 2008/12/19

Y1 - 2008/12/19

N2 - 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.

AB - 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.

KW - Cancer therapy

KW - Lung lymph flow

KW - Nitric-oxide

KW - Transvascular fluid flux

KW - Vascular leakage

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

Abstract

Keywords

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