title: Cathelicidin deficiency predisposes to eczema herpeticum.
abstract: BACKGROUND
  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).
  
  
  OBJECTIVE
  This study investigated the potential role of cathelicidins in host susceptibility to HSV infection.
  
  
  METHODS
  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).
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Allergy and Immunology, Department of Pediatrics, National Jewish Medical and Research Center, Denver, Colorado 80206, USA.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Howell
authors.forename: Andreas
authors.initials: A
authors.lastname: Wollenberg
authors.forename: Richard L
authors.initials: RL
authors.lastname: Gallo
authors.forename: Michael
authors.initials: M
authors.lastname: Flaig
authors.forename: Joanne E
authors.initials: JE
authors.lastname: Streib
authors.forename: Cathy
authors.initials: C
authors.lastname: Wong
authors.forename: Tatjana
authors.initials: T
authors.lastname: Pavicic
authors.forename: Mark
authors.initials: M
authors.lastname: Boguniewicz
authors.forename: Donald Y M
authors.initials: DY
authors.lastname: Leung
mesh_terms: D000328:Adult; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000172:deficiency* / Q000235:genetics / Q000276:immunology / Q000494:pharmacology; D001483:Base Sequence; D004279:DNA, Viral / Q000235:genetics; D003876:Dermatitis, Atopic / Q000150:complications / Q000276:immunology; D018258:Herpesvirus 2, Human / Q000187:drug effects / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology; D006801:Humans; D007113:Immunity, Innate; D007073:Immunoglobulin E / Q000097:blood; D007617:Kaposi Varicelliform Eruption / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D011994:Recombinant Proteins / Q000494:pharmacology; D014779:Virus Replication / Q000187:drug effects; D054804:Cathelicidins
chemical_list: D023181:Antimicrobial Cationic Peptides; D004279:DNA, Viral; D011994:Recombinant Proteins; D007073:Immunoglobulin E; D054804:Cathelicidins