The kappa-opioid agonist, asimadoline, alters cytokine gene expression in adjuvant arthritis

Objective. We have previously found that the kappa -opioid agonist, asimado line, attenuates adjuvant arthritis in a dose-dependent, antagonist-reversi ble manner. To elucidate possible mechanisms, we investigated the effects o f asimadoline (5 mg/kg/day i.p.) or vehicle on in vivo cytokine expression and T-cell recruitment in adjuvant arthritis. Methods. Arthritis severity was assessed every 3-4 days for 21 days. Rats w ere killed on days 0, 13 and 21 post-induction and synovial membrane and in guinal lymph nodes were removed for mRNA extraction. Changes in cytokine mR NA expression were measured using reverse transcription-polymerase chain re action (RT-PCR) and densitometry. T cells in joints were quantified by immu nohistochemistry. Results. Asimadoline significantly decreased arthritis severity at day 13, with a concomitant decrease in synovial membrane expression of cytokines in terleukin-17 and transforming growth factor-beta (TGF-beta) mRNA at day 13, and no change in T cell numbers in the joints of arthritic rats. By contra st, in the inguinal lymph nodes, expression of tumour necrosis factor was i ncreased at day 13 and TGF-beta mRNA was increased throughout. Conclusion. An altered balance, therefore, in the pro- and anti-inflammator y effects of TGF-beta by asimadoline might explain its striking anti-arthri tic actions.