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

Abstract

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-beta (TGF-beta) 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-beta mRNA was increased throughout.

CONCLUSION:

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

• Authors: K A Bush, B W Kirkham, J S Walker
• Journal: Rheumatology (Oxford, England) (Rheumatology (Oxford)) Vol. 40 Issue 9 Pg. 1013-21 (Sep 2001) ISSN: 1462-0324 [Print] England
• PMID: 11561112 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Acetamides
• Adrenergic alpha-Agonists
• Cytokines
• Pyrrolidines
• RNA, Messenger
• RNA
• asimadoline

Topics

• Acetamides (pharmacology, therapeutic use)
• Adrenergic alpha-Agonists (pharmacology, therapeutic use)
• Animals
• Ankle Joint (drug effects, metabolism)
• Arthritis, Experimental (drug therapy, genetics, metabolism)
• Cell Count
• Cytokines (biosynthesis, genetics)
• Disease Models, Animal
• Gene Expression (drug effects)
• Immunoenzyme Techniques
• Lymph Nodes (drug effects, metabolism)
• Male
• Pyrrolidines (pharmacology, therapeutic use)
• RNA (analysis)
• RNA, Messenger (metabolism)
• Rats
• Reverse Transcriptase Polymerase Chain Reaction
• Synovial Membrane (drug effects, metabolism)
• T-Lymphocytes (cytology, drug effects)