PHILADELPHIA — Isotretinoin appears to derive its effectiveness from increased production of the antimicrobial protein neutrophil-gelatinase associated lipocalin in the skin, reducing sebum levels, and in turn reducing levels of Propionibacterium acnes, according to new data.
While isotretinoin is the most effective agent for patients with moderate to severe acne, the drug's teratogenicity makes alternative therapies desirable. A better understanding of the drug's mechanism of action could direct the investigation of new therapies, Kimberly Lumsden, an MD/PhD student at Pennsylvania State University, Hershey, said at the annual meeting of the Society for Pediatric Dermatology.
In vivo neutrophil-gelatinase associated lipocalin (NGAL) levels are highest 1 week after the start of isotretinoin treatment.
In addition, the study showed that in vivo sebum and P. acnes levels start to decrease during the first week of treatment with isotretinoin and continue to decrease for up to 8 weeks.
Dr. Lumsden and her colleagues recruited a patient on isotretinoin and evaluated the level of NGAL present on the skin using a tape-stripping method at weeks 1, 4, and 8.
“At 1 week we saw the greatest increase in the level of NGAL, which levels off at 4–8 weeks,” she said.
Next, they used recombinant NGAL protein and solution with P. acnes in vitro to determine if isotretinoin is antibacterial. They found a dose response. Increasing NGAL concentration led to decreased survival of P. acnes.
For the last phase, they recruited a cohort of nine patients to try to determine whether decreases in sebum and P. acnes coincide with the initial increase in NGAL levels with isotretinoin.
“We did see a decrease in sebum at 1 week and it's further decreased by 8 weeks,” she said.
However, sebum levels start to recover by about 8 weeks. As for P. acnes, there was a trend toward decreased levels at week 1 and levels continued to decrease through weeks 4 and 8.