Isotretinoin therapy changes the expression of antimicrobial peptides in acne vulgaris.

In acne vulgaris, antimicrobial peptides (AMPs) could play a dual role; i.e., protective by acting against Propionibacterium acnes, pro-inflammatory by acting as signalling molecules. The cutaneous expression of 15 different AMPs was investigated in acne patients; furthermore, the impact of isotretinoin therapy on AMP expression was analysed in skin biopsies from 13 patients with acne vulgaris taken before, during and after a 6-month treatment cycle with isotretinoin using quantitative real-time polymerase chain reaction. Cutaneous expression of the AMPs cathelicidin, human ß-defensin-2 (HBD-2), lactoferrin, lysozyme, psoriasin (S100A7), koebnerisin (S100A15), and RNase 7 was upregulated in untreated acne vulgaris, whereas α-defensin-1 (HNP-1) was downregulated compared to controls. While relative expression levels of cathelicidin, HBD-2, lactoferrin, psoriasin (S100A7), and koebnerisin (S100A15) decreased during isotretinoin treatment, only those of cathelicidin and koebnerisin returned to normal after 6 months of isotretinoin therapy. The increased expression of lysozyme and RNase 7 remained unaffected by isotretinoin treatment. The levels of granulysin, RANTES (CCL5), perforin, CXCL9, substance P, chromogranin B, and dermcidin were not regulated in untreated acne patients and isotretinoin had no effect on these AMPs. In conclusion, the expression of various AMPs is altered in acne vulgaris. Isotretinoin therapy normalizes the cutaneous production of distinct AMPs while the expression of others is still increased in healing acne. Considering the antimicrobial and pro-inflammatory role of AMPs, these molecules could serve as specific targets for acne therapy and maintenance of clinical remission.

Does isotretinoin therapy of acne cure or cause depression?

Cosmetic defects in acne may provoke a wide range of mental disorders (depressive, social-phobic, etc.). Isotretinoin is a very effective acne treatment; hence, it usually resolves the associated mental disorders. However, more available data show the possible association of taking isotretinoin and the onset of a depressive syndrome that includes frank depression and even suicidal ideation. The frequency of depressive disorders during isotretinoin treatment varies from 1% to 11% in different studies, and it is unclear whether this is a consequence of isotretinoin therapy. Since it crosses the blood-brain barrier, isotretinoin affects the expression of a broad spectrum of genes in the limbic structures, thus affecting the function of the dopaminergic, serotonergic, and noradrenergic neurons involved in the regulation of mood and emotion. It was suggested that isotretinoin in high concentrations inhibits hippocampal neurogenesis and induces apoptosis of hippocampal cells. However, some studies do not confirm this pathogenic role, and isotretinoin was even reported to have a therapeutic effect in acne-associated depression. In this review, we highlight epidemiological data, the underlying molecular pathogenesis, and the aspects of prevention concerning retinoid-induced depression in acne from the practical point of view of a dermatologist.