Photodynamic therapy; a comparison with other immunomodulatory treatments of adjuvant-enhanced arthritis in MRL-lpr mice

Abstract

SUMMARYAlthough numerous experimentat immunomodulalory regimens have been reported lo be effective in the treatment of rheumatoid arthritis, they also produce undesirable side effects. An alternative specific modality of localized treatment is photodynamic therapy (PDT). In this study we treated 13-week-old MRL-tpr mice whose spontaneous arthritis was enhanced by intradermal injection o\' Freund's complete adjuvant (FCA). One group received transcutaneous photodynamic therapy at days D. 10, and 20, following the F^CA injection. The other group.s were injected with 1 nig. kg per day indomethacin, 40 mg/kg per day cyclosporin A (CsA), or treated with 3 Gy sublethal whole body irradiation (WBI). The development of swelling was monitored for I month, at which time proteinurca, tymphadenopathy and the histopathology of the joints and kidneys were assessed. The results demonstrated that PDTand the conventional treatments significantly ameliorated swelling of the hindlimbs from H)"^,< in the untreated FCA-injected animals to below the 19';^. level characteristic of the unmanipulated control. Histological examination showed a reduction in pannus lornialion, and cartilage and bone destruetion, the characteristics of adjuvant-enhanced arthritis. PDT did not affect the survival rate, lymphoproliferation, or proteinuria of the treated animals. However, indomethacin increased proteinurea. and was less eflcctive in preventing cartilage and bone destruction, hurlhermore, lower doses of CsA and WBI exacerbated arthritis activity. These results indicate that photodynamic therapy can inhibit the development of adjuvant-enhanced arthritis in MRL-tpr mice with similar effectiveness to the conventional treatments, but without their negative side effects.

Photodynamic therapy: illuminating the road from cell death towards anti-tumour immunity

“…Clinical improvement in patients with severe steroid-refractory GVHD [171,172] Clinical improvement in both acute and chronic GVHD patients with skin and visceral involvement [172][173][174][175] Psoriasis ALA-local irradiation No or very poor clinical efficacy in plaque psoriasis patients. Frequent occurrence of severe pain at the site of illumination [176,177] ALA-local irradiation Clinical improvement in patients with plaque psoriasis [178][179][180][181] ALA-local irradiation Mild to moderate improvement in patients with palmoplantar pustular psoriasis [182] Methylene blue-local irradiation Complete response in patients with resistant plaque psoriatic lesions [183] Methyl-ALA-local irradiation No superior results of PDT in the treatment of nail psoriasis comparing with pulse dye laser light exposure in patients [184] Psoriatic arthritis BPD-MA-half or total body irradiation with UVA Safe and well-tolerated treatment, alleviation of the disease and significant pain reduction in 5 out of 17 patients [185] Rheumatoid arthritis m-THPC-local irradiation A potent method of synovectomy in a rat model [186] Polymeric photosensitiser prodrug targeting thrombin-local irradiation Selective and minimally invasive synovectomy in mice, promising results in primary human synoviocytes in vitro [187] m-THPC-local irradiation Significant reduction of arthritic score in mice [188] BPD-MA-PDT-local irradiation Selective destruction of synovium in an antigeninduced arthritis in rabbits [189] BPD-MA-PDT-total body irradiation Alleviation of signs of Freund's complete adjuvant-induced arthritis in mice [190] Scleroderma Topical ALA-local irradiation Good therapeutic response in PUVA-resistant patients, no carcinogenic potential compared with PUVA [191][192][193] ATX-S10(Na)-PDT Enhanced modulation of dermal matrix components compared with ALA-PDT in vitro. [194] Alopecia areata Topical ALA-local irradiation An ineffective approach in AA.…”

Photodynamic therapy induces an immune response against a bacterial pathogen

“…In 1994 Ratkay et al performed a study to compare the effect of PDT and other immunomodulatory treatments in adjuvant-enhanced arthritis in MRL-lpr mice [70]. The arthritis was induced with two intradermal injections of Freud’s adjuvant supplemented with heat-inactivated, lyophilized Mycobacteria tubercolosis .…”

In vitro resistance of articular chondrocytes to 5‐Aminolevulinic acid based photodynamic therapy

“…The inflammatory response, and as a consequence the destruction of cartilage, could be reduced successfully in experimental animal studies and in humans [1][2][3][4][5][6][7][8][9][10]. This anti-inflammatory effect was attributed to the inactivation and/or ablation of the inflamed synovial tissue, which was targeted by PDT.…”