PHOTODYNAMIC THERAPY - A COMPARISON WITH OTHER IMMUNOMODULATORY TREATMENTS OF ADJUVANT-ENHANCED ARTHRITIS IN MRL-LPR MICE

Although numerous experimental immunomodulatory regimens have been rep orted to be effective in the treatment of rheumatoid arthritis, they a lso produce undesirable side effects. An alternative specific modality of localized treatment is photodynamic therapy (PDT). In this study w e treated 13-week-old MRL-lpr mice whose spontaneous arthritis was enh anced by intradermal injection of Freund's complete adjuvant (FCA). On e group received transcutaneous photodynamic therapy at days 0, 10, an d 20, following the FCA injection. The other groups were injected with 1 mg/kg per day indomethacin, 40 mg/kg per day cyclosporin A (CsA), o r treated with 3 Gy sublethal whole body irradiation (WBI). The develo pment of swelling was monitored for 1 month, at which time proteinurea , lymphadenopathy and the histopathology of the joints and kidneys wer e assessed. The results demonstrated that PDT and the conventional tre atments significantly ameliorated swelling of the hindlimbs from 70% i n the untreated FCA-injected animals to below the 19% level characteri stic of the unmanipulated control. Histological examination showed a r eduction in pannus formation, and cartilage and bone destruction, the characteristics of adjuvant-enhanced arthritis. PDT did not affect the survival rate, lymphoproliferation, or proteinuria of the treated ani mals. However, indomethacin increased proteinurea, and was less effect ive in preventing cartilage and bone destruction. Furthermore, lower d oses of CsA and WBI exacerbated arthritis activity. These results indi cate that photodynamic therapy can inhibit the development of adjuvant -enhanced arthritis in MRL-lpr mice with similar effectiveness to the conventional treatments, but without their negative side effects.