Doxycycline treatment for rosacea reduced the antimicrobial peptide cathelicidin and protease activity in skin, and these reductions correlated with clinical improvement.
Cathelicidin ↓ correlated with clinical successReduced cathelicidin expression and protease activity at 12 weeks predicted treatment response in rosacea patients on doxycycline
What the researchers found
Doxycycline 40-mg modified-release capsules significantly reduced inflammatory lesions and improved investigator global assessment scores compared to placebo over 12 weeks. Cathelicidin expression and protein levels decreased during treatment. Low levels of protease activity and cathelicidin expression at 12 weeks correlated with treatment success. Low baseline protease activity predicted clinical response to doxycycline, suggesting it could serve as a predictive biomarker for treatment selection.
Why it matters
Cathelicidin is an antimicrobial peptide that plays a dual role — it protects against infection but drives inflammation when overproduced, as in rosacea. This study validates cathelicidin as both a disease mechanism and a trackable biomarker, demonstrating that reducing this peptide correlates with clinical improvement. This supports a precision medicine approach to rosacea treatment.
How the study worked
A multicenter, randomized, double-blind, placebo-controlled trial enrolled 170 adults with papulopustular rosacea. Participants received doxycycline 40-mg modified-release capsules or placebo for 12 weeks. Cathelicidin expression and protease activity were measured from stratum corneum tape strips and skin biopsies from a random subset. Clinical response was assessed by inflammatory lesion counts and investigator global assessment scores.
What this study cannot tell us
Healthy control subjects were not studied, so baseline cathelicidin levels in unaffected skin were not compared. Skin biopsies were only obtained from a subset of participants. The 12-week duration may not capture long-term effects or relapse patterns. The study used sub-antimicrobial dose doxycycline, so results may not apply to higher antibiotic doses.
How to read the evidence
This is a multicenter, randomized, double-blind, placebo-controlled trial published in the Journal of the American Academy of Dermatology, a top dermatology journal. The study design is strong, though the biomarker analysis was limited to a subset of participants.
When this study was published
Published in 2016, this study is about a decade old but remains a landmark reference for cathelicidin's role as a rosacea biomarker. The findings continue to inform current understanding of antimicrobial peptides in skin disease.
The bigger picture
Cathelicidin (LL-37) is one of the most studied antimicrobial peptides in human skin biology. Its role in rosacea pathogenesis has been known for years, but this trial provides clinical trial-level evidence linking cathelicidin reduction to treatment success. Understanding how endogenous peptides drive skin inflammation opens avenues for targeted therapies that modulate peptide activity rather than broadly suppressing immune function.
Questions still open
- Could directly targeting cathelicidin overproduction with peptide-based therapies treat rosacea more specifically than doxycycline?
- Do cathelicidin levels rebound after stopping doxycycline, and does this predict rosacea relapse?
- Can baseline cathelicidin or protease levels be used clinically to select the best treatment for individual rosacea patients?
Common questions
What is cathelicidin and why is it important in rosacea?
Why was the doxycycline dose so low in this study?
Read the original research
Improved clinical outcome and biomarkers in adults with papulopustular rosacea treated with doxycycline modified-release capsules in a randomized trial.
Journal of the American Academy of Dermatology, 74(6), 1086-92
Citation
Di Nardo, Anna; Holmes, Anna D; Muto, Yumiko; Huang, Eugene Y; Preston, Norman; Winkelman, Warren J; Gallo, Richard L. (2016). Improved clinical outcome and biomarkers in adults with papulopustular rosacea treated with doxycycline modified-release capsules in a randomized trial.. Journal of the American Academy of Dermatology, 74(6), 1086-92. https://doi.org/10.1016/j.jaad.2016.01.023