title: Low dose endoluminal photodynamic therapy improves murine T cell-mediated colitis.
abstract: OBJECTIVE
  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/cm (2); 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Nutrition and Health Department, Nestle Research Centre, Lausanne, Switzerland.
authors.forename: L
authors.initials: L
authors.lastname: Favre
authors.forename: F
authors.initials: F
authors.lastname: Borle
authors.forename: D
authors.initials: D
authors.lastname: Velin
authors.forename: D
authors.initials: D
authors.lastname: Bachmann
authors.forename: H
authors.initials: H
authors.lastname: Bouzourene
authors.forename: G
authors.initials: G
authors.lastname: Wagnieres
authors.forename: H
authors.initials: H
authors.lastname: van den Bergh
authors.forename: P
authors.initials: P
authors.lastname: Ballabeni
authors.forename: T
authors.initials: T
authors.lastname: Gabrecht
authors.forename: P
authors.initials: P
authors.lastname: Michetti
authors.forename: S
authors.initials: S
authors.lastname: Schreiber
authors.forename: M-A
authors.initials: MA
authors.lastname: Ortner
mesh_terms: D000622:Aminolevulinic Acid / Q000008:administration & dosage*; D000818:Animals; D017209:Apoptosis; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000502:physiology; D003092:Colitis / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D003113:Colonoscopy; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D051379:Mice; D008807:Mice, Inbred BALB C; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000008:administration & dosage*; D016133:Polymerase Chain Reaction; D013601:T-Lymphocytes
chemical_list: D016207:Cytokines; D017319:Photosensitizing Agents; D000622:Aminolevulinic Acid