Role of proinflammatory cytokines in a toxic response: application of cytokine knockout mice in toxicological research.
The toxic effect of xenobiotics may be direct or mediated through the release of secondary toxic mediators such as proinflammatory cytokines. Knockout mice (KO or -/-) with discrete gene deletions obtained by homologous recombination may prove the function of a given cytokine in general and in toxico-pathogenesis. The technology is briefly described, and a short review of the phenotype of mice with deletions of several proinflammatory cytokines is given. The emphasis of this presentation is on the role of tumor necrosis factor, interleukins and interferon-gamma in endotoxic shock and acute phase response. The future application of these mice for mechanistic studies in toxicological research is discussed.
Ryffel
B
B
Institute of Toxicology of the University of Zürich, Switzerland.
D000210:Acute-Phase Reaction / Q000378:metabolism; D000818:Animals; D016207:Cytokines / Q000235:genetics / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D012772:Shock, Septic / Q000209:etiology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000502:physiology; D015262:Xenobiotics / Q000633:toxicity*
D016207:Cytokines; D014409:Tumor Necrosis Factor-alpha; D015262:Xenobiotics