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Rheumatology 2001; 40: 1013-1021
© 2001 British Society for Rheumatology

Original Papers

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

K. A. Bush, B. W. Kirkham1 and J. S. Walker

School of Physiology and Pharmacology, University of New South Wales and
1 Department of Rheumatology, St George Hospital, New South Wales, Australia

Objective. We have previously found that the {kappa}-opioid agonist, asimadoline, attenuates adjuvant arthritis in a dose-dependent, antagonist-reversible manner. To elucidate possible mechanisms, we investigated the effects of 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 were killed on days 0, 13 and 21 post-induction and synovial membrane and inguinal lymph nodes were removed for mRNA extraction. Changes in cytokine mRNA expression were measured using reverse transcription–polymerase chain reaction (RT–PCR) and densitometry. T cells in joints were quantified by immunohistochemistry.

Results. Asimadoline significantly decreased arthritis severity at day 13, with a concomitant decrease in synovial membrane expression of cytokines interleukin-17 and transforming growth factor-ß (TGF-ß) mRNA at day 13, and no change in T cell numbers in the joints of arthritic rats. By contrast, in the inguinal lymph nodes, expression of tumour necrosis factor was increased at day 13 and TGF-ß mRNA was increased throughout.

Conclusion. An altered balance, therefore, in the pro- and anti-inflammatory effects of TGF-ß by asimadoline might explain its striking anti-arthritic actions.

KEY WORDS: Cytokines, Opioids, Asimadoline, Adjuvant arthritis, {kappa}-Opioid agonist, Inflammation.

Correspondence to: J. Walker, School of Physiology and Pharmacology, Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia, 2052


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