ABSTRACT
Rheumatoid arthritis (RA) is a systemic immune-mediated in©ammatory disease (IMID) of the joints and has been associated with multifaceted pathogenic pathways. These may include aberrant T cells, B cells, macrophages, and dendritic cells, as well as an unbalanced network of chemokines and cytokines, with tumor necrosis factor-α (TNF-α) playing a key role (Kuek, Hazleman, and Ostor 2007). Although the pathophysiology of RA is complex, several anti-in©ammatory agents provide transient symptomatic relief. These include the use of immunotoxic agents (e.g., methotrexate), nonsteroidal anti-in©ammatory drugs (e.g., selective cyclo-oxygenase-2 inhibitors), synthetic glucocorticoids, and biological agents that suppress the activity of TNF-α (Turini and DuBois 2002; Wislowska and Jakubicz 2007; Cronstein 2005; Czock et al. 2005). All existing therapies have signi‰cant limitations, which include anergy to prolonged treatment, systemic immune suppression, bone loss, gastrointestinal bleeding, and high cost (Callen 2007; Chen et al. 2009; Kong, Teuber, and Gershwin 2006; Song et al. 2005). Dozens of candidate compounds targeting enzymes, receptors, and signaling molecules critically involved at various points in the in©ammatory cascade are either currently in clinical development or have recently been approved (Kukar, Petryna, and Efthimiou 2009; Storage, Agrawal, and Furst 2010; Yurchenko et al. 2010; Serhan, Chiang,
Introduction ....................................................................................................................................207 Adrenal Insuf‰ciency in Rheumatoid Arthritis and Relation to DHEA Metabolism ....................209
