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
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]).


CONCLUSIONS
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.
Lopes-Martins
Rodrigo Alvaro Brandão
RA
Laboratory of Pharmacology and Phototherapy, Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, Cidade Universitária Armando de Salles Oliveira, Brazil.
Albertini
Regiane
R
Lopes-Martins
Patrícia Sardinha Leonardo
PS
de Carvalho
Flávio Aimbire Soares
FA
Neto
Hugo Caire Castro Faria
HC
Iversen
Vegard Vereide
VV
Bjordal
Jan Magnus
JM
D000818:Animals; D006727:Hormone Antagonists / Q000494:pharmacology*; D006854:Hydrocortisone / Q000037:antagonists & inhibitors*; D007249:Inflammation / Q000628:therapy*; D008027:Light; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D015735:Mifepristone / Q000494:pharmacology*; D010998:Pleurisy / Q000628:therapy; D011897:Random Allocation
D006727:Hormone Antagonists; D015735:Mifepristone; D006854:Hydrocortisone