Antiinflammatory role of endomorphins in osteoarthritis, rheumatoid arthritis, and adjuvant-induced polyarthritis.
OBJECTIVE
Pain sensitization and the related secretion of neuropeptides from sensory nerve terminals are proinflammatory in osteoarthritis (OA), rheumatoid arthritis (RA), and adjuvant-induced polyarthritis. In contrast, endogenous opioids such as the recently discovered endomorphins (EMs) are antiinflammatory. However, the role of endogenous EMs such as EM-1 and EM-2 has never been investigated in OA and RA.


METHODS
We established a highly sensitive radioimmunoassay to detect EM-1 and EM-2. In patients with RA and patients with OA, immunohistochemistry for EM-1 and EM-2 was performed, and double-staining was used to identify EM-positive cells. The effects of EM-1 and EM-2 on the secretion of interleukin-6 (IL-6) and IL-8 from human synovial tissue were studied by tissue superfusion, and the therapeutic effects of EM-1 were tested in a rat model of adjuvant-induced polyarthritis.


RESULTS
EM-positive cells were located in the sublining area and vessel walls but were particularly evident in the highly inflamed lining area. Human macrophages, T cells, and fibroblasts stained positive for EMs. The synovial density of EM-positive cells was higher in patients with OA than in those with RA. EM-1 inhibited synovial secretion of IL-6 in patients with RA and secretion of IL-8 in patients with RA and those with OA (maximum 10(-10)M). EM-2 inhibited IL-8 secretion only from RA tissue (maximum 10(-10)M). In rats with adjuvant-induced polyarthritis, thymus, spleen, and synovial tissue contained significantly more EM-1 than was observed in controls. Rats with adjuvant-induced polyarthritis benefited from EM-1 treatment.


CONCLUSIONS
EM-1 had antiinflammatory effects in patients with OA or RA and in a model of adjuvant-induced polyarthritis. Local enhancement of EM-1 might be an interesting therapeutic option in different forms of arthritis.
Straub
Rainer H
RH
Department of Internal Medicine I, University Hospital, Regensburg, Germany. rainer.straub@klinik.uni-regensburg.de
Wolff
Christine
C
Fassold
Alexander
A
Hofbauer
Rafael
R
Chover-Gonzalez
Antonio
A
Richards
Louise J
LJ
Jessop
David S
DS
D000368:Aged; D001168:Arthritis / Q000276:immunology*; D001169:Arthritis, Experimental / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000276:immunology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000276:immunology* / Q000378:metabolism; D010003:Osteoarthritis / Q000276:immunology; D013583:Synovial Membrane / Q000276:immunology / Q000378:metabolism
D015850:Interleukin-6; D016209:Interleukin-8; D009842:Oligopeptides; C105293:endomorphin 1; C105294:endomorphin 2