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Iron homeostasis and nitric oxide (NO) biology are reciprocally interconnected. Iron affects the expression of inducible or type 2 NO synthase 2 (iNOS or NOS2) by negatively modulating the binding affinity of the iron-sensitive tran-scription regulators hypoxia-inducible factor (HIF) and nuclear factor (NF)-IL6 to their re-spective consensus sequences within the Nos2 promoter (Weiss et al., 1994; Melillo et al., 1997; Dlaska and Weiss 1999). This is important to the host immune response because NOS2 is a major component of the antimicrobial effec-tor machinery, and the formation of NO by macrophages has been shown to mediate protec-tion from infections with a myriad of pathogens, including viruses, bacteria, protozoa, and para-sites (MacMicking et al., 1997; Bogdan, 2001). Some of these effects have been linked to direct cellular toxicity exerted by the labile radical NO and its chemical congeners, which are gener-ated upon interaction with reactive oxygen in-termediates (Stamler and Hausladen, 1998). In addition, the high affinity of NO for iron leads to targeting of heme and nonheme iron and destabilization of iron-sulfur clusters within th