Photodynamic therapy as a novel therapeutic approach for the treatment of Crohn's disease
Photodynamic therapy (PDT) may modify the mucosal immune response and thus serve as a therapy for Crohn’s disease (CD). After evaluating safety in BALB/c mice and establishing an endoscopic index of colitis (EIC), we could demonstrate that a single «low dose» PDT with 15 mg/kg delta-aminolevulinic acid and 10 J/cm2 induced healing of the colitis and decreased the expression indices of pro-inflammatory cytokines. The effect of «low dose» PDT appeared more rapidly, was stronger and lasted longer in the context of higher colitis activity. Before testing «low dose» PDT in humans we evaluated in dose-response experiments the effect on healing of colitis and safety with higher (20J/cm2) and lower (2J/cm2) energy doses. The lower PDT dose regimen induced an improvement of the EIC three days after PDT compared to disease control mice (p< 0.05). The improvement after three days was weaker with 2 J/cm2 than with the previously used energy dose of 10J/cm2. The higher PDT dose regimen did not induce an improvement of the EIC compared to control disease mice. Both regimens were safe. Furthermore, the effect of a second «low dose» PDT with 10J/cm2 performed one week after the first session was assessed. The second PDT delayed recurrence of inflammation compared to mice with a single PDT treatment (1 week p < 0.05, 2 weeks p = 0.01). To further evaluate the immunomodulatory effect of PDT we performed an immunostaining of activated T-cells (CD4+ T-cells) in the mucosa of the colon, measured the percentage of Annexin V+ cells (an early marker of apoptosis) and performed Propidium iodide (PI) staining to identify viable cells. Three days after «low dose» PDT a diminution in the number of CD4+ cells compared to disease control mice was seen. The percentage of Annexin V+ cells within the CD4+/PI- population increased after PDT treatment compared to disease control mice (p<0.01). In conclusion, «low dose» PDT improves colitis, decreases expression indices of proinflammatory cytokines and leads to disappearance of activated CD4+T-cells in the mucosa of the colon. The diminution of pathogenic CD4+ T-cells is likely to be partly mediated by apoptosis. The greatest effect on healing of colitis was achieved with the primarily chosen energy dose of 10 J/cm2. A second PDT prolongs remission. In view of the favorable effect in mice, «low dose» PDT is now being tested in humans.
Record created on 2014-02-06, modified on 2016-08-09