TY - JOUR
T1 - Suppression of adjuvant arthritis by κ-opioid receptor agonist
T2 - Effect of route of administration and strain differences
AU - Antić, Jelena
AU - Vasiljević, Tatjana
AU - Stanojević, Stanislava
AU - Vujić, Vesna
AU - Kovačević-Jovanović, Vesna
AU - Djergović, Danica
AU - Miljević, Čedo
AU - Marković, Branislav M.
AU - Radulović, Jelena
PY - 1996/9
Y1 - 1996/9
N2 - It is well established that κ-opioid receptor agonists exert antiinflammatory and antihyperalgesic effects during nonspecific inflammation as well as suppressive effects on the development of humoral and cell-mediated immune responses to foreign antigens. The aim of this study was to investigate the ability of the κ-opioid receptor agonist MR 2034 to modulate adjuvant arthritis in the rat. In the first series of experiments, treatments of Wistar rats were performed using several routes of drug administration: intraperitoneal (ip), intracaudal (ic), intracerebroventricular (icv) and intraplantar (ipl). MR 2034 significantly suppressed joint swelling after ip and ic treatment, slightly reduced inflammation after ipl treatment, and did not produce any effect after icv treatment. In the second series of experiments, the suppressive effect of ip injected MR 2034 was investigated using Wistar, Dark August (DA) and Lewis rats. In Wistar rats, MR 2034 significantly decreased the incidence of adjuvant arthritis, and suppressed mean joint score and aggregate joint score. Similarly, in DA rats treated with MR 2034, mean arthritic score was significantly suppressed, but other clinical parameters were not affected. In Lewis rats, however, ip treatment with MR 2034 failed to produce any suppressive effect on joint disease and even potentiated the initial development of arthritis. These data suggest that immunosuppressive and antiinflammatory action of MR 2034 markedly depend on the route of drug administration and strain susceptibility to opioids.
AB - It is well established that κ-opioid receptor agonists exert antiinflammatory and antihyperalgesic effects during nonspecific inflammation as well as suppressive effects on the development of humoral and cell-mediated immune responses to foreign antigens. The aim of this study was to investigate the ability of the κ-opioid receptor agonist MR 2034 to modulate adjuvant arthritis in the rat. In the first series of experiments, treatments of Wistar rats were performed using several routes of drug administration: intraperitoneal (ip), intracaudal (ic), intracerebroventricular (icv) and intraplantar (ipl). MR 2034 significantly suppressed joint swelling after ip and ic treatment, slightly reduced inflammation after ipl treatment, and did not produce any effect after icv treatment. In the second series of experiments, the suppressive effect of ip injected MR 2034 was investigated using Wistar, Dark August (DA) and Lewis rats. In Wistar rats, MR 2034 significantly decreased the incidence of adjuvant arthritis, and suppressed mean joint score and aggregate joint score. Similarly, in DA rats treated with MR 2034, mean arthritic score was significantly suppressed, but other clinical parameters were not affected. In Lewis rats, however, ip treatment with MR 2034 failed to produce any suppressive effect on joint disease and even potentiated the initial development of arthritis. These data suggest that immunosuppressive and antiinflammatory action of MR 2034 markedly depend on the route of drug administration and strain susceptibility to opioids.
KW - Adjuvant arthritis
KW - Immunosuppression
KW - Rat strains
KW - κ-Opioid agonist
UR - http://www.scopus.com/inward/record.url?scp=0030245662&partnerID=8YFLogxK
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U2 - 10.1016/0162-3109(96)00114-2
DO - 10.1016/0162-3109(96)00114-2
M3 - Article
C2 - 8886854
AN - SCOPUS:0030245662
SN - 0162-3109
VL - 34
SP - 105
EP - 112
JO - Immunopharmacology
JF - Immunopharmacology
IS - 2-3
ER -