Steroid receptor antagonist mifepristone inhibits the anti-inflammatory effects of photoradiation

Objective: We designed an animal pleurisy study to assess if the anti-inflammatory effect of photoradiation could be affected by concomitant use of the cortisol antagonist mifepristone. Background Data: Although interactions between photoradiation and pharmacological agents are largely unknown, parallel use of steroids and photoradiation is common in the treatment of inflammatory disorders such as arthritis and tendinitis. Methods: Forty BALB/c male mice were randomly divided in five groups. Inflammation was induced by carrageenan administered by intrathoracic injections. Four groups received carrageenan, and one control group received injections of sterile saline solution. At 1, 2, and 3 h after injections, photoradiation irradiation was performed with a dose of 7.5 J/cm(2). Two of the carrageenan-injected groups were pre-treated with orally administered mifepristone. Results: Total leukocyte cell counts revealed that in carrageenan-induced pleurisy, photoradiation significantly reduced the number of leukocyte cells (p < 0.0001, mean 34.5 [95% CI: 32.8-36.2] versus 87.7 [95% CI: 81.0-94.4]), and that the effect of photoradiation could be totally blocked by adding the cortisol antagonist mifepristone (p < 0.0001, mean 34.5 [95% CI: 32.1-36.9] versus 82.9 [95 % CI: 70.5-95.3]). Conclusion: The steroid receptor antagonist mifepristone significantly inhibited the anti-inflammatory effect of photoradiation. Commonly used glucocorticoids are also known to down-regulate steroid receptors, and further clinical studies are necessary to elucidate how this interaction may decrease the,effect size of photoradiation over time. For this reason, we also suggest that, until further clinical data can be provided, clinical photoradiation trials should exclude patients who have received steroid therapy within 6 months before recruitment.