Topical aminolaevulinic acid-photodynamic therapy produces an inflammatory infiltrate but reduces Langerhans cells in healthy human skin in vivo

Br J Dermatol. 2011 Sep;165(3):513-9. doi: 10.1111/j.1365-2133.2011.10433.x.

Abstract

Background: Topical photodynamic therapy (PDT) elicits a therapeutic response in both skin cancer and immune-mediated skin disorders. While PDT induces direct cell death, host inflammatory and immune responses to PDT may contribute to the therapeutic effects.

Objectives: To examine the impact of topical PDT on leucocyte trafficking and mediators of chemotaxis in healthy human skin.

Methods: Aminolaevulinic acid (ALA)-PDT was performed on the buttock skin of seven healthy volunteers. Biopsies for immunohistochemical assessment were taken 1, 4 and 24 h post-PDT and from untreated contralateral buttock skin (baseline).

Results: A significant dermal neutrophilic infiltrate appeared early, peaking at 4 h (P < 0·01) and returning to near baseline by 24 h. Expression of E-selectin was significantly higher at 4 h (P < 0·05) and correlated strongly with neutrophil numbers (r = 0·93). Expression of intercellular adhesion molecule 1 was significantly elevated after 24 h (P < 0·05) with an apparent gradual increase in CD4+ T cells up to this time point. Notably, epidermal Langerhans cells were significantly reduced 24 h post-PDT compared with baseline (P < 0·01) and comprised a significantly larger proportion of cells with migratory rather than dendritic morphology (P < 0·05). The number of epidermal cells expressing tumour necrosis factor-α significantly increased at 4 h (P < 0·05) and remained elevated 24 h post-PDT, whereas no significant change in expression of interleukin (IL)-1β or IL-8 was seen.

Conclusions: Reduction of Langerhans cells by topical PDT of human skin may play a significant role in PDT-induced local immunosuppression, potentially benefiting the treatment of immune-mediated skin disorders but negatively impacting on antitumour responses. Further exploration according to disease indication/treatment protocol is warranted.

MeSH terms

  • Administration, Topical
  • Adult
  • Aminolevulinic Acid / administration & dosage
  • Aminolevulinic Acid / pharmacology*
  • Buttocks
  • Cell Movement / drug effects
  • Cytokines / metabolism
  • E-Selectin / metabolism
  • Female
  • Humans
  • Langerhans Cells / drug effects*
  • Male
  • Neutrophils / drug effects
  • Photochemotherapy / methods*
  • Photosensitizing Agents / administration & dosage
  • Photosensitizing Agents / pharmacology*
  • Skin / cytology*
  • Skin / drug effects
  • T-Lymphocytes / drug effects
  • Young Adult

Substances

  • Cytokines
  • E-Selectin
  • Photosensitizing Agents
  • Aminolevulinic Acid