期刊
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
卷 377, 期 3, 页码 786-791出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2008.10.066
关键词
Cancer therapy; Lung lymph flow; Nitric-oxide; Transvascular fluid flux; Vascular leakage
资金
- National Institutes of Health [GM066312]
- Shriners of North America [8820, 8450]
- Inotek Pharmaceuticals Corporation, Beverly, MA, USA
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. (C) 2008 Elsevier Inc. All rights reserved.
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