Saquinavir‐NO Inhibits IL‐6 Production in Macrophages. (18th June 2014)

• Record Type: Journal Article
• Authors: Momčilović, Miljana; Mangano, Katia; Jevtić, Bojan; Mammana, Santa; Stošić‐Grujičić, Stanislava; Nicoletti, Ferdinando; Miljković, Djordje
• Is Part Of: Basic & clinical pharmacology & toxicology. Volume 115:Number 6(2014:Jun.)
• Page Start: 499
• Page End: 506
• Publication Date: 2014-06-18
• Subjects: Pharmacology -- Periodicals; Toxicology -- Periodicals; Pharmacology -- Periodicals; Toxicology -- Periodicals; Pharmacology, Clinical -- Periodicals; Computer network resources; Electronic journals; 615.1
• DOI: 10.1111/bcpt.12268
• Languages: English
• ISSNs: 1742-7835

Abstract

<abstract abstract-type="main" id="bcpt12268-abs-0001"> <title>Abstract</title> <p>Covalent attachment of the nitric oxide (NO) moiety to the HIV protease inhibitor Saquinavir (Saq) produced a new chemical entity, named Saquinavir‐NO, (Saq‐NO) with reduced toxicity and potent immunoregulatory influence on T lymphocytes. In this study, we have compared head‐to‐head the effects of Saq‐NO and Saq on mouse and rat peritoneal macrophage cytokine secretion and NO production upon <italic>in vitro, ex vivo</italic> and <italic>in vivo</italic> conditions. The results demonstrate that Saq‐NO, but not Saq, potently decreased interleukin (IL)‐10, IL‐6 and nitrite accumulation and increased the levels of IL‐1β and tumour necrosis factor (TNF) in supernatants of mouse and rat macrophage cultures <italic>in vitro</italic>. Treatment of mice with Saq‐NO, but not Saq, inhibited <italic>ex vivo</italic> secretion of IL‐6 from macrophages. Consistent with these findings, Saq‐NO also reduced blood levels of IL‐6 in lipopolysaccharide‐treated mice. The observed inhibitory influence of Saq‐NO on IL‐6 generation in macrophages may be involved in the observed antitumour and immunomodulatory effects of the drug.</p> </abstract>