Endoscopy 2011; 43(7): 604-616
DOI: 10.1055/s-0030-1256382
Original article

© Georg Thieme Verlag KG Stuttgart · New York

Low dose endoluminal photodynamic therapy improves murine T cell-mediated colitis

L.  Favre1 , F.  Borle2 , D.  Velin3 , D.  Bachmann3 , H.  Bouzourene4 , G.  Wagnieres2 , H.  van den Bergh2 , P.  Ballabeni5 , T.  Gabrecht2 , P.  Michetti3 , S.  Schreiber6 , M.-A.  Ortner7
  • 1Nutrition and Health Department, Nestle Research Centre, Lausanne, Switzerland
  • 2Photomedicine Group, Swiss Federal Institute of Science and Technologies (EPFL), Lausanne, Switzerland
  • 3Department of Gastroenterology and Hepatology, University Hospital (CHUV), Lausanne, Switzerland
  • 4Institute of Pathology, University Hospital (CHUV), Lausanne, Switzerland
  • 5Institute of Social and Preventive Medicine, University Hospital (CHUV), Lausanne, Switzerland
  • 6Institute of Clinical Molecular Biology, Christian-Albrechts University, Kiel, Germany
  • 7Department of Gastroenterology, DMLL, University Hospital “Inselspital” Bern, Switzerland
Further Information

Publication History

submitted 30 September 2008

accepted after revision 31 January 2011

Publication Date:
27 May 2011 (online)

Preview

Background and study aims: Low dose photodynamic therapy (LDPDT) may modify the mucosal immune response and may thus provide a therapy for Crohn’s disease. We evaluated the efficacy and safety of this technique in a murine T cell-mediated colitis model.

Methods: The safety of LDPDT was first tested in BALB/c mice. Naïve T cells were used to induce colitis in mice with severe combined immunodeficiency, which were followed up endoscopically, and a murine endoscopic index of colitis (MEIC) was developed. The efficacy of LDPDT (10 J/cm2; delta-aminolevulinic acid, 15 mg/kg bodyweight) was then tested on mice with moderate colitis, while a disease control group received no treatment. The MEIC, weight, length, and histology of the colon, cytokine expression indices, number of mucosal CD4+ T cells, percentage of apoptotic CD4+ T cells, body weight, and systemic side effects were evaluated.

Results: LDPDT improved the MEIC (P = 0.011) and the histological score (P = 0.025), diminished the expression indices of the proinflammatory cytokines, interleukin-6 (P = 0.042), interleukin-17 (P = 0.029), and interferon-gamma (P = 0.014), decreased the number of mucosal CD4+ T cells, and increased the percentage of apoptotic CD4+ T cells compared with the disease control group. No local or systemic side effects occurred.

Conclusion: LDPDT improves murine T cell-mediated colitis, decreases the proinflammatory cytokines interleukin-6, interleukin-17, and interferon-gamma, and decreases the number of CD4+ T cells. No adverse events were observed. Therefore, this technique is now being evaluated in patients with inflammatory bowel disease.

References

M.-A. OrtnerMD 

Department of Gastroenterology, DMLL
University Hospital “Inselspital” Bern

Murtenstrasse
CH-3010 Bern
Germany

Fax: +41-31-6329765

Email: ma.ortner@bluewin.ch