NF-κB in defense and disease ciated with inflammatory disease. Indeed, as discussed by Tak and Firestein (this Perspective series), NF-κB is activated in the inflamed synovium of rheumatoid arthritis patients (8) as well as in the synovium of animal models of this disease (9). Interestingly, inhibition of NF-κB inhibited the inflammation in a bacterial cell wall model for arthritis (9). The fact that NF-κB regulates TNF-α expression and is a key effector of this cytokine is consistent with the development of therapies aimed at blocking TNF as a therapy for rheumatoid arthritis. NF-κB activation is assumed to lie at the heart of other inflammatory diseases, such as asthma (1), and has been shown to be required for development of inflammatory bowel disease in an animal model (10). Thus, the ability of NF-κB to activate transcription of genes encoding cell adhesion molecules (ICAM-1, VCAM-1, E-selectin) and chemoattractant proteins (monocyte chemoattractant protein-1 [MCP-1]) would lead to the recruitment of inflammatory cells to the lung, a hallmark of asthma (11). Additionally, NF-κB appears to be an effector, downstream of TNF-α, in euthyroid sick syndrome (12) and in cachexia (13). The Perspective by Tak and Firestein in this series focuses on the role of NF-κB in inflammatory disorders, whereas the Perspective by Zhang and Ghosh focuses on the key role of NF-κB in promoting innate immune responses. These two articles clearly illustrate the “good and evil” aspects of NF-κB whereby NF-κB is required for immunological mechanisms but detrimental when it is dysregulated.

Consistent with its essential role in inflammation, NF-κB is known to be the target of anti-inflammatory compounds (see ref. 11). Thus, it has been reported that aspirin and other nonsteroidal anti-inflammatory drugs block NF-κB (14–16). Glucocorticoids such as prednisone have been shown to block NF-κB activation by different mechanisms in different cell types (11, 17). In fact, other anti-inflammatory compounds used in therapy have been shown to inhibit NF-κB. For example, gold compounds used as antiarthritic thera-