Blue light special: ALA-PDT safe and effective tool for treating acne lesions

Brooklyn, N.Y. — Recent research has shown that ALA-PDT using blue light is a safe and effective treatment for acne vulgaris.

ALA (Levulan) is absorbed by the skin and changes into a compound that is sensitive to light. ALA-PDT is a combination of a topical solution followed by exposure to blue light from the Blue Light Photodynamic Therapy Illuminator (BLU-U)
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The combination of ALA and PDT is believed to preferentially target Propionibacterium acnes (P.acnes) and sebaceous glands. Research
Wei-Li Lee, Ph.D., director of research, department of dermatology at the State University of New York (SUNY)-Downstate, Brooklyn, N.Y., and colleagues conducted an in vitro study to investigate the effects of ALA-PDT on cytokine production in cultured keratinocytes.
If complexity of a cytokine network’s regulation is an index of its biological importance, then IL-1 ranks as an extraordinarily important cytokine.

Skin is unique in that a significant reservoir of pre-formed IL-1 alpha exists in epidermis in situ. Both intact epidermis and stratum corneum contain significant IL-1 bioactivity, leading to the concept that epidermis is a shield of sequestered IL-1 surrounding the host, waiting to be released upon injury.

External stimuli, such as wounding, burns, UV radiation or chemical insults, along with internal stimuli such as local cytokine release from stimulated leukocytes, can induce the release of IL-1 for local or systemic delivery.

"The expression of cytokines such as IL-1 alpha plays a critical role in the development of inflammation and results in the expression of dermal and vascular adhesion molecules, chemoattraction of inflammatory cells, and stimulation of other mediators of inflammation," Dr. Lee Ph.D. tells Dermatology Times.

In vitro experiments
In the in vitro experiments, immortalized keratinocytes (hTERT cells. Rheinwald Lab) and primary keratinocytes (NHEK – normal human epithelial keratinocytes) were used. They were grown to subconfluence and treated with several concentrations of ALA ranging from 1 mM to 0.1 nM before being illuminated with narrow band blue light (NBBL at 405-420 nm) and/or treated with cytokines such as IFN-gamma (5-10 U/ml) and TNF-alpha (2.5-25ng/ml).

Efforts were made to mimic the therapeutic milieu of clinical trials, including exposure to ALA, incubation time, and dose used for NBBL exposure. ELISA was performed to detect pro-inflammatory cytokines IL-1 alpha and ICAM-1.

Results
Study results showed that treatment with ALA or BL alone is not cytotoxic to NHEK and hTERT keratinocytes. However, the combination of ALA with cytokines (IFN-gamma, TNF-alpha) caused cell death ranging from 27 to 48 percent. Adding NBBL to ALA and cytokines produced increased cell death ranging from 56 to 62 percent.
Based on MTT assays, all tested concentrations of ALA were equivalently cytotoxic.
The ELISA data demonstrated that ALA up-regulated the IL-1 alpha level whereas NBBL reduced the IL-1 alpha level; induction of IL-1 alpha by ALA with or without NBBL is not significantly dose-dependent. NBBL decreased IL-1alpha production when used alone (Shnitkind & Lee, J Drugs Derm 2006 5 (7): 605); this suppressive effect was lost when used in combination with ALA or with both ALA and cytokines (IFN-gamma + TNF-alpha).

Comparison
Comparison of IL-1 alpha production in NHEK and hTERT cells showed that the magnitude of up-regulation is higher in hTERT. When ALA was added to cytokines/NBBL treated cells, there was about a twofold increase in IL-1 alpha in NHEK cells and an up to five-fold increase production of IL-1 alpha in hTERT cells. The authors also noted that ICAM-1 upregulation was similar to IL-1 alpha.
The department of dermatology at SUNY-Downstate was one of the multicenter sites selected to study the effect of ALA-PDT therapy in treating patients (248 subjects) with moderate-to-severe acne.

Adverse Effects
According to Dr. Lee, side effects such as burning, stinging, and redness have been reported and are probably related to the cell cytotoxicity and increased IL-1 alpha level in the epidermis. Post-treatment efficacy evaluations show that patients remain well controlled up to three months following their last treatment.

"Though there is still some fine-tuning that needs to be done with ALA-PDT in the treatment of acne, this line of therapy is very important in light of the current and increasing worry clinicians have with prolonged use of systemic antibiotics and the risks of isotretinoin therapy.

"Acne therapy with ALA-PDT offers a different treatment approach and a possible treatment solution, especially for inflammatory acne,” Dr. Lee says.