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 | |
| State | Published - 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
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 journal › Article
}
TY - JOUR
T1 - Lung-protective effects of the metalloporphyrinic peroxynitrite decomposition catalyst WW-85 in interleukin-2 induced toxicity
AU - Maybauer, Dirk M.
AU - Maybauer, Marc O.
AU - Szabo, 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
AU - Traber, Daniel L.
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
UR - http://www.scopus.com/inward/record.url?scp=56049085330&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=56049085330&partnerID=8YFLogxK
U2 - 10.1016/j.bbrc.2008.10.066
DO - 10.1016/j.bbrc.2008.10.066
M3 - Article
C2 - 18951875
AN - SCOPUS:56049085330
VL - 377
SP - 786
EP - 791
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
IS - 3
ER -