Interleukin-2 (IL-2), a cytokine that induces natural killer cells termed lymphokine-activated killer (LAK) cells, is in use as an anticancer agent. During IL-2 therapy, adverse effects, such as vasodilatation and hypotension, are common. Previous studies suggest that these effects are due to nitric oxide (NO). Therefore a model of IL-2-induced hyperdynamic response in sheep was developed to test the effect of pyridoxalated haemoglobin polyoxyethylene conjugate (PHP; a NO scavenger), which is currently in clinical development for the treatment of shock associated with systemic inflammatory response syndrome. Twelve female sheep were divided into four groups (n=3 per group): sham control (Ringer's lactate solution), PHP alone (20 mg·kg-1·h-1 for 96 h), IL-2 alone (recombinant human IL-2; 1440000 units/kg intravenously every 8 h) and a combination of PHP and IL-2. All of the sheep received Ringer's lactate solution to maintain haematocrit at baseline levels. The sheep had free access to food and water. A fall in the mean arterial pressure and systemic vascular resistance index by 20% was observed in the IL-2 group, but not in the PHP+IL-2 group. The fluid requirement to maintain the haematocrit was higher in the IL-2 group (5 ml·kg-1·h-1) than in the PHP+IL-2 group (4 ml·kg-1·h-1). The sham group showed no changes in any of the parameters. Scavenging NO by PHP prevented the hyperdynamic reaction induced by IL-2 administration in sheep. This activity of PHP may prevent the early discontinuation of IL-2 therapy that results because of these adverse events.
Pyridoxalated haemoglobin polyoxyethylene conjugate, a nitric oxide scavenger, decreases dose-limiting hypotension associated with interleukin-2 (IL-2) therapy
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Kazunori MURAKAMI, Chris PRIVALLE, Perenlei ENKHBAATAR, Katsumi SHIMODA, Frank C. SCHMALSTIEG, Joseph DEANGELO, Steve LEE, Lillian D. TRABER, Daniel L. TRABER; Pyridoxalated haemoglobin polyoxyethylene conjugate, a nitric oxide scavenger, decreases dose-limiting hypotension associated with interleukin-2 (IL-2) therapy. Clin Sci (Lond) 1 November 2003; 105 (5): 629–635. doi: https://doi.org/10.1042/CS20030164
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