**1. Introduction**

172 Rheumatoid Arthritis – Treatment

Zagon, I.S., Wu, Y., McLaughlin, P.J. (1997). Opioid growth factor is present in human and

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mouse gastrointestinal tract and inhibits DNA synthesis. *Am J Physiol* 272 (4Pt 2):

The mechanism of arthritis including rheumatoid arthritis (RA) has not been clarified enough in terms of its molecular biology. However, owing to advances in techniques to produce monoclonal antibodies and genetic engineering techniques to produce recombinant proteins, targeted therapies have progressed. Tumor necrosis factor-alpha (TNF-), interleukin-1 (IL-1), interleukin-6 (IL-6), and T-cells (CD28) are representative targets, and therapies targeting them have produced epoch-making results in the treatment of RA. In this text, we report the role and effects of therapy with adrenomedullin as a novel, promising targeted therapy.

Adrenomedullin (ADM) is a peptide that was discovered by the assay-based monitoring of platelet cAMP activity (Kitamura et al., 1993). This protein shows not only marked vasodilatory but also *in vivo* and *in vitro* anti-inflammatory activities (Isumi et al., 1998).

To determine the efficacy of ADM in patients with RA, we researched the plasma level of ADM and its correlation with the plasma CRP level. The result showed that the plasma ADM level in patients with RA was twice that in healthy controls and strongly correlated with the blood CRP level, and the ADM level in synovial tissue in patients with RA was 3 times that in patients with osteoarthritis (Chosa et al., 2003). Then, thorough research is needed to examine whether the cultured RA synoviocytes are related to the ADM *in vitro*. The result showed that ADM was produced from RA synoviocytes and reduced the IL-6 level in cultured media (Fig. 5). These results suggest the close involvement of ADM in arthritis in RA. Therefore, to examine the therapeutic efficacy of intra-articular ADM injection, we injected ADM into the joint of a rabbit model of adjuvant arthritis, and confirmed the inhibition of arthritis at an early stage. These findings suggest the potentiality of ADM as a novel drug for the treatment of arthritis in RA (Okura et al., 2008).
