Signaling sphingolipids are biomarkers for atopic dermatitis prone to disseminated viral infections.

Background: Life-threatening viral diseases such as eczema herpeticum (EH) and eczema vaccinatum (EV) occur in <5% of individuals with atopic dermatitis (AD). The diagnosis of AD, however, excludes all individuals with AD from smallpox vaccination.

Objectives: We sought to identify circulatory and skin lipid biomarkers associated with EH and EV.

Ankyrin repeat domain 1 regulates innate immune responses against herpes simplex virus 1: A potential role in eczema herpeticum.

Background: Atopic dermatitis (AD) is a common inflammatory skin disease. A subset of patients with AD are susceptible to disseminated herpes simplex virus (HSV) infection, a complication termed eczema herpeticum (ADEH+). The immune mechanisms causing ADEH+ remain elusive.

Skin Wound Healing Is Accelerated by a Lipid Mixture Representing Major Lipid Components of Chamaecyparis obtusa Plant Extract.

In chronic nonhealing wounds, the healing process is disrupted and wounds are often infected with bacteria. About 85% of lower extremity amputations in diabetes are attributed to deep infection of foot ulcers. Therefore, infection control is critical for wound care.

The signal transducer and activator of transcription 6 gene (STAT6) increases the propensity of patients with atopic dermatitis toward disseminated viral skin infections.

Background: Atopic dermatitis (AD) is a chronic inflammatory skin disease associated with increased susceptibility to recurrent skin infections.

Objective: We sought to determine why a subset of patients with AD have an increased risk of disseminated viral skin infections.

Methods: Human subjects with AD with a history of eczema herpeticum (EH) and various control groups were enrolled.

Human atopic dermatitis complicated by eczema herpeticum is associated with abnormalities in IFN-γ response.

Background: The basis for increased susceptibility of patients with atopic dermatitis (AD) to develop disseminated viral skin infections such as eczema herpeticum (AD with a history of eczema herpeticum, ADEH(+)) is poorly understood.

Objective: We sought to determine whether subjects with AD prone to disseminated viral skin infections have defects in their IFN responses.

Methods: GeneChip profiling was used to identify differences in gene expression of PBMCs from patients with ADEH(+) compared with patients with AD without a history of eczema herpeticum (ADEH(-)) and nonatopic controls.

Specificity protein 1 is pivotal in the skin's antiviral response.

Background: Previous studies have found specificity protein (Sp) 1 transcription factor in the viral replication machinery and postulated that Sp1 was required for viral replication in host cells.

Objectives: We investigated the role of Sp1 in the skin's antiviral responses from the perspective of host defense and its biological relevance in patients with atopic dermatitis and a history of eczema herpeticum (ADEH(+)).

Methods: Small interfering RNA duplexes were used to knock down Sp1 in keratinocytes.

Inhibition of S100A11 gene expression impairs keratinocyte response against vaccinia virus through downregulation of the IL-10 receptor 2 chain.

Background: The mechanism that predisposes patients with atopic dermatitis (AD) to disseminated vaccinia viral (VV) skin infection after smallpox vaccination is unknown. We have demonstrated that expression of S100A11, a calcium-binding protein involved in keratinocyte differentiation, is downregulated in AD.

Objective: We investigated whether inhibiting expression of S100A11 increased VV replication in human keratinocytes and the mechanism by which S100A11 affects the innate immune response of keratinocytes.

Ceragenins: a class of antiviral compounds to treat orthopox infections.

Eczema vaccinatum is a potentially fatal, disseminated viral skin infection that develops in individuals with atopic dermatitis after exposure to the vaccinia virus (VV). Despite advances in modern medicine, there are few options for those suffering from disseminated VV infections. Ceragenins (CSAs) are synthetic antimicrobial compounds designed to mimic the structure and function of endogenous antimicrobial peptides (AMPs).

Macrophage inflammatory protein 3alpha deficiency in atopic dermatitis skin and role in innate immune response to vaccinia virus.

Background: Patients with atopic dermatitis (AD) are prone to disseminated viral skin infections and therefore are not vaccinated against smallpox because of potential complications. Macrophage inflammatory protein 3alpha (MIP-3alpha) is a C-C chemokine expressed by keratinocytes that exhibits antimicrobial activity against bacteria and fungi; however, its role in antiviral innate immunity is unknown.

Objective: Evaluate the level of MIP-3alpha in AD skin and its role in the innate immune response to vaccinia virus (VV).

Cathelicidin deficiency predisposes to eczema herpeticum.

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.

Cytokine milieu of atopic dermatitis skin subverts the innate immune response to vaccinia virus.

Atopic dermatitis (AD) is associated with eczema vaccinatum (EV), a disseminated viral skin infection that follows inoculation with vaccinia virus (VV). This study examined whether AD skin can control VV replication, and the role of IL-4 and IL-13 in modulating the human cathelicidin LL-37, an antimicrobial peptide that kills VV. AD skin exhibited increased VV replication and decreased LL-37 expression compared to normal or psoriasis skin.

Structure-function relationships among human cathelicidin peptides: dissociation of antimicrobial properties from host immunostimulatory activities.

Cathelicidins and other antimicrobial peptides are deployed at epithelial surfaces to defend against infection. These molecules have broad-spectrum killing activity against microbes and can have effects on specific mammalian cell types, potentially stimulating additional immune defense through direct chemotactic activity or induction of cytokine release. In humans, the cathelicidin hCAP18/LL-37 is processed to LL-37 in neutrophils, but on skin it can be further proteolytically processed to shorter forms.

Selective killing of vaccinia virus by LL-37: implications for eczema vaccinatum.

Possible bioterrorism with smallpox has led to the resumption of smallpox (vaccinia virus) immunization. One complication, eczema vaccinatum, occurs primarily in patients with atopic dermatitis (AD). Skin lesions of patients with AD, but not psoriasis, is deficient in the cathelicidin antimicrobial peptide (LL-37) and human beta-defensin-2 (HBD-2).

Complement activation in a model of chronic fatigue syndrome.

Background: A need exists to identify biological markers in chronic fatigue syndrome (CFS).

Objective: To use an exercise and/or allergen challenge to induce the symptoms of CFS and to identify a biological marker that correlates with these symptoms.

Methods: Patients with CFS (n = 32) and age-matched, normal control patients (n = 29) exercised for 20 minutes on a stationary bike at 70% of their predicted max work load (Watts).