title: Endomorphins in rheumatoid arthritis, osteoarthritis, and experimental arthritis.
abstract: The opioid tetrapeptides endomorphins (EM)-1 and EM-2 are widely expressed in central nervous system and immune tissues of rats and humans. Their analgesic properties are well characterized but they also have anti-inflammatory properties. EM-1 significantly attenuated the onset of hindpaw inflammation in adjuvant-induced arthritis in rats. Immunohistochemical staining demonstrated the presence of EMs in T cells, macrophages, and fibroblasts in synovial tissues from patients with osteo- or rheumatoid arthritis (RA). In an ex vivo superfusion system, EM-1 potently inhibited the release of proinflammatory cytokines interleukin (IL)-6 and IL-8 from synovial tissues from patients with osteo- or RA. These results demonstrate that EMs are endogenously synthesized within human immune cells and have the potential to act as potent therapeutic agents in the treatment of chronic inflammatory disease. We discuss the clinical potential for EM analogues chemically modified to resist proteolytic degradation and identify modified protease-resistant analogues with enhanced bioactivity.
authors.affiliation: Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology, University of Bristol, Bristol, UK. david.jessop@bristol.ac.uk
authors.forename: David S
authors.initials: DS
authors.lastname: Jessop
authors.forename: Alexander
authors.initials: A
authors.lastname: Fassold
authors.forename: Christine
authors.initials: C
authors.lastname: Wolff
authors.forename: Rafael
authors.initials: R
authors.lastname: Hofbauer
authors.forename: Antonio
authors.initials: A
authors.lastname: Chover-Gonzalez
authors.forename: Louise J
authors.initials: LJ
authors.lastname: Richards
authors.forename: Rainer H
authors.initials: RH
authors.lastname: Straub
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000276:immunology* / Q000378:metabolism; D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D009842:Oligopeptides / Q000276:immunology* / Q000378:metabolism; D010003:Osteoarthritis / Q000276:immunology* / Q000378:metabolism; D051381:Rats
chemical_list: D009842:Oligopeptides; C105293:endomorphin 1; C105294:endomorphin 2