Premium
Saquinavir‐ NO Inhibits IL ‐6 Production in Macrophages
Author(s) -
Momčilović Miljana,
Mangano Katia,
Jevtić Bojan,
Mammana Santa,
StošićGrujičić Stanislava,
Nicoletti Ferdinando,
Miljković Djordje
Publication year - 2014
Publication title -
basic and clinical pharmacology and toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.805
H-Index - 90
eISSN - 1742-7843
pISSN - 1742-7835
DOI - 10.1111/bcpt.12268
Subject(s) - in vivo , saquinavir , ex vivo , cytokine , pharmacology , in vitro , chemistry , nitric oxide , tumor necrosis factor alpha , lipopolysaccharide , secretion , interleukin , macrophage , microbiology and biotechnology , biology , biochemistry , immunology , endocrinology , human immunodeficiency virus (hiv) , viral load , antiretroviral therapy
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 in vitro, ex vivo and in vivo 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 in vitro . Treatment of mice with Saq‐ NO , but not Saq, inhibited ex vivo 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.