Cathelicidin deficiency predisposes to eczema herpeticum.
Howell. Michael D MD; Wollenberg. Andreas A; Gallo. Richard L RL; Flaig. Michael M; Streib. Joanne E JE; Wong. Cathy C; Pavicic. Tatjana T; Boguniewicz. Mark M; Leung. Donald Y M DY
Key Findings
- LL‑37 directly kills HSV at concentrations found in normal skin.
- Mice lacking the cathelicidin gene have higher HSV replication in skin than normal mice.
- Human eczema herpeticum patients have lower skin LL‑37 levels than atopic dermatitis patients without HSV infection.
- Higher serum IgE correlates with lower skin LL‑37 expression.
Practical Outcomes
- Boosting LL‑37 in the skin could help prevent herpes outbreaks in people with eczema. Strategies that raise LL‑37—such as vitamin D supplementation, topical vitamin D analogs, or certain skin‑care ingredients—might be worth trying, especially for those with high IgE. However, specific dosing or protocols are not yet established, so start with safe, low‑dose approaches and monitor skin response.
Summary
The natural skin peptide LL‑37 can kill herpes simplex virus (HSV) and people with atopic dermatitis who have low LL‑37 are more likely to get severe HSV skin infections (eczema herpeticum). Higher blood IgE levels tend to go with lower LL‑37, so IgE might hint at who’s at risk.
Abstract
The cathelicidin family of antimicrobial peptides is an integral component of the innate immune response that exhibits activity against bacterial, fungal, and viral pathogens. Eczema herpeticum (ADEH) develops in a subset of patients with atopic dermatitis (AD) because of disseminated infection with herpes simplex virus (HSV). This study investigated the potential role of cathelicidins in host susceptibility to HSV infection. Glycoprotein D was measured by means of real-time RT-PCR as a marker of HSV replication in skin biopsy specimens and human keratinocyte cultures. Cathelicidin expression was evaluated in skin biopsy specimens from patients with AD (n = 10) without a history of HSV skin infection and from patients with ADEH (n = 10). The cathelicidin peptide LL-37 (human cathelicidin) exhibited activity against HSV in an antiviral assay, with significant killing (P < .001) within the physiologic range. The importance of cathelicidins in antiviral skin host defense was confirmed by the observation of higher levels of HSV-2 replication in cathelicidin-deficient (Cnlp-/-) mouse skin (2.6 +/- 0.5 pg HSV/pg GAPDH, P < .05) compared with that seen in skin from their wild-type counterparts (0.9 +/- 0.3). Skin from patients with ADEH exhibited significantly (P < .05) lower levels of cathelicidin protein expression than skin from patients with AD. We also found a significant inverse correlation between cathelicidin expression and serum IgE levels (r2 = 0.46, P < .05) in patients with AD and patients with ADEH. This study demonstrates that the cathelicidin peptide LL-37 possesses antiviral activity against HSV and demonstrates the importance of variable skin expression of cathelicidins in controlling susceptibility to ADEH. Additionally, serum IgE levels might be a surrogate marker for innate immune function and serve as a biomarker for which patients with AD are susceptible to ADEH. A deficiency of LL-37 might render patients with AD susceptible to ADEH. Therefore increasing production of skin LL-37 might prevent herpes infection in patients with AD.
Study Information
pubmed
2006
2006-02-14T00:00:00.000Z
10.1016/j.jaci.2005.12.1345