Selenium mediates a switch in macrophage polarization

Selenium (Se) is important for optimal functioning of the immune system (Ebert-Dumig et al., 1999; Kiremidjian-Schumacher and Roy, 1998; Kubena and McMurray, 1996; McKenzie et al., 1998). Several studies demonstrate Se deficiency to be associated with impaired immune responsiveness, and Se-supplementation results in increased immunocompetence (McKenzie et al., 1998). For example, Se supplementation significantly increased tumor cytotoxicity of macrophages and natural killer cells (Kubena and McMurray, 1996). Selenium deficiency has been associated with several pathological conditions, including cardiovascular diseases (Azoicai et al., 1997), rheumatoid arthritis (Knekt et al., 2000), AIDS (Hori et al., 1997), systemic inflammatory response syndrome (SIRS) (Kocyigit et al., 2004; Qujeq et al., 2003; Sakr et al., 2007), and most notably cancer (Combs, 1999; Ganther, 1999), for which oxidative stress and inflammation appear to be the common denominators. It has been proposed that Se, in the form of selenoproteins, mitigates inflammation in addition to preventing malignant transformation of cells (Ganther, 1999). In fact, an investigation of the causal relationship between Se in forage crops and county levels of cancer mortality in the United States and cancer mortality rates for the major cancer sites were found to be higher in counties with low Se (Clark et al., 1991; Rayman, 2000, 2002). Selenium intake may be suboptimal with respect to disease risk, notably in the population of adults in the United Kingdom, Europe, China, and New Zealand. Moreover, with the changes in lifestyle and food habits, plasma Se levels appear to be on the downward trend, tilting more toward deficiency. Particularly in cigarette smokers, HIV, and breast cancer patients, the plasma Se levels were significantly reduced (Cole et al., 2005; Fleming, 1989; Preston, 1991). Heyland et al. (2005) conducted a meta-analysis demonstrating the correlation between plasma Se levels and tissue inflammation, infection, and organ failure. This study also showed that Se supplementation was associated with lowered mortality rate. Studies by Sakr et al. (2007) suggested a correlation between decreased plasma Se levels and multiorgan dysfunction with SIRS or septic shock. Angstwurm et al. (2007) reported the ability of selenite (1000 µg IV) to improve survival of patients with SIRS, sepsis, and septic shock.