“Neutrophils are also thought to be important contributors to the inflammation seen in rosacea. Their presence may be explained, in part, by Demodex mites, which act as a chemotactic factor for neutrophils, and neutrophils release IL-17.”
IL-17 also stimulates production of cathelicidin, which is relevant to rosacea because cathelicidin is a chemotactic factor and has angiogenic properties. In addition, IL-17 induces expression of matrix metalloproteinase-9 (MMP-9) that is also implicated in the pathogenesis of rosacea.
A review of the cellular and molecular mechanisms underlying the anti-inflammatory effects of standard treatments for rosacea show that they all act on the IL-17 pathway by either inhibiting the production of downstream inflammatory mediators or inhibiting cytokines that promote differentiation of Th17 cells and, therefore, the production of IL-17, Dr. Vender says.
For example, metronidazole decreases Demodex counts and may directly and indirectly impair induction of IL-17 through its actions on other cytokines and chemokines. A relationship between ivermectin and IL-17 may include its antiparasitic action on Demodex, but ivermectin also decreases the production of cytokines that are induced by IL-17.
Doxycycline blocks secretion of kallikrein and cytokines induced by IL-17 as well as the activity and production of MMP-9. Azelaic acid inhibits the UV-induced upregulation of inflammatory cytokines that are induced by IL-17. Cyclosporine, which is used topically in the treatment of ocular rosacea, also inhibits the production of IL-17 through suppression of Th17 cells.
Dr. Vender has received grants and/or research support from companies that market IL-17 inhibitors and treatments for rosacea. He received no financial support for the research, authorship or publication of his article on IL-17 and rosacea.
Amir ali A, Vender R, Vender R. The Role of IL-17 in Papulopustular Rosacea and Future Directions. J Cutan Med Surg. 2019;:1203475419867611.