PMID: 9544427Apr 17, 1998Paper

The role of nitric oxide in interleukin-2 therapy induced hypotension

Cancer Metastasis Reviews
H Shahidi, R G Kilbourn

Abstract

Nitric oxide is an uncharged free radical that mediates a range of physiologic processes in the vasculature. As a principal determinant of vascular tone, the overproduction of nitric oxide has been implicated in the pathogenesis of sepsis- and cytokine-induced hypotension. The enzyme that produces nitric oxide, nitric oxide synthase, exists in three isoforms. One of the three isoforms, inducible nitric oxide synthase, is expressed in many cell types only after stimulation by cytokines and/or endotoxin. Compared to the constitutive nitric oxide synthase enzymes, the inducible enzyme generates larger quantities of nitric oxide for longer periods. Expression of the inducible isoform in vitro requires stimulation by a mixture of cytokines including interferon-gamma, tumor necrosis factor-alpha, and interleukin-1 beta. These proinflammatory cytokines are known mediators of sepsis and are also produced in the serum of cancer patients during interleukin-2 therapy, thereby leading to excessive production of nitric oxide. Interleukin-2 therapy is associated with a spectrum of cardiovascular toxicities and hemodynamic alterations that are indistinguishable from those seen in septic shock. Many of these hemodynamic effects have been linke...Continue Reading

Citations

Aug 21, 2002·Biological & Pharmaceutical Bulletin·George HsiaoJoen-Rong Sheu
May 17, 2002·The American Journal of Gastroenterology·Giovanni LatellaRenzo Caprilli
May 22, 2003·Journal of the National Cancer Institute·Alan L EpsteinLeslie A Khawli
Jun 16, 2010·Proceedings of the National Academy of Sciences of the United States of America·Carsten KriegOnur Boyman
Jan 29, 2000·Journal of Medicinal Chemistry·J E SaavedraL K Keefer

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