Biol. Pharm. Bull. 30(6) 1140—1143 (2007)

is characterized by the chronic inflammation and hyperproliferation of synovial cells in multiple joints. Proinflammatory cytokines and chemokines produced by synoviocytes and infiltrated immune cells are implicated in the disease pathogenesis, such as production of proteases and reactive oxygen intermediates, proliferation of synovial fibroblasts, cartilage degradation, infiltration of inflammatory cells and angiogenesis. Antibody against TNFa , soluble receptor for TNFa , interleukin-1 receptor antagonist (IL-1ra) and antibody against IL-6 appeared to be effective in the treatment of RA patients, indicating that these cytokines are pivotal in the pathogenesis of the disease. These cytokines form a network, such as the induction of IL-1 and IL-6 by TNFa , and IL-6 induction by IL-1. Fibroblast-like synoviocytes are major cells that produce IL-1 and IL-6, and TNFa is probably produced by macrophages. There are two types of IL-1, IL-1a and IL-1b . They bind to the same receptor, type I IL-1 receptor, and transduce intracellular signaling. IL-1 contributes to the pathogenesis of the disease by affecting fibroblast-like synovial cells and cartilage to induce matrix metalloproteases (MMPs), NO and prostaglandin E2, which accelerate cartilage degradation. IL1 also inhibits the synthesis of type II collagen from cartilage. By the experiments using animal model of arthritis IL-1a appeared to be important in the early phase of arthritis and participates in the inhibition of proteoglycan synthesis. Although it is not clarified how and what causes RA, RA is deviated to women as also observed in other autoimmune diseases; the ratio of RA incidence in women to men is about 4 : 1. The levels of estrogen to androgen in synovial fluid are elevated in both male and female RA patients and the level of testosterone in serum and synovial fluid is lower in male RA patients as compared to normal individuals. Therefore, sex hormones are implicated in the gender difference of RA. In this study, we examined the effect of 5a-dihydrotestosterone (DHT) on the induction of IL-1a mRNA by TNFa , and suggested that DHA inhibits the effect of TNFa by inhibiting NF-kB activation in a manner dependent on the androgen receptor (AR).