Relationship between Cytokines and Spinal mu Opioid Receptor Expression during Adjuvant-induced Arthritis in Rats

Abstract

Aims: It is now clear that cytokines such as interleukins play a fundamental role in inflammatory processes. Cytokines now offer alternative targets for therapeutic intervention and may be useful as predictive biomarkers of disease. In this study, we aimed to evaluate the relationship between cytokines and spinal mu opioid receptor expression during adjuvant-induced arthritis (AA) in rats. Methodology: AA was induced by a single subcutaneous injection of CFA into the rats’ hindpaw. Anti-IL-6 and IL- 10 were administered daily during the 21 days of study. Hyperalgesia and edema were assessed on days 0, 3, 7, 14 and 21 by radiant heat and plethysmometer respectively. Spinal mu opioid receptor (MOR) expression was detected by Western blotting. Results: Daily administration of neutralizing doses of anti-IL-6 caused a significant decrease in serum IL-10 level in AA rats, while treatment with anti-IL10 antibody in the AA rats did not significantly change serum IL-6 level. Anti-IL-10 antibody administration caused a significant increase in paw edema and hyperalgesia, while anti-IL-6 treatment decreased heperalgesia on days 3 and 7 but caused a significant increased in hyperalgesia on days 14 and 21 in AA rats. Administration of neutralizing dose of anti-IL10 antibody in AA rats did not cause significant variation of spinal MOR expression in comparison to IL-6 antibody treatment which induced significant reduction in spinal MOR expression. Conclusion: Together these results suggest that some of the anti-hyperalgesic effects of serum IL-6 during the chronic phase of inflammation may be mediated by increased IL-10 levels.