Decreased serum LL-37 and vitamin D3 levels in atopic dermatitis: relationship between IL-31 and oncostatin M.
Kanda. N N; Hau. C S CS; Tada. Y Y; Sato. S S; Watanabe. S S
Key Findings
- AD patients show reduced serum LL‑37 and 25‑hydroxyvitamin D compared to healthy controls
- Active vitamin D (1,25‑dihydroxyvitamin D3) stimulates LL‑37 production in keratinocytes and neutrophils
- LL‑37 and vitamin D enhance oncostatin M and IL‑31 release from activated T‑cells, while vitamin D lowers IL‑22 production
Practical Outcomes
- Maintain adequate vitamin D status (e.g., 2,000‑4,000 IU/day depending on baseline levels) to support natural LL‑37 production, which may improve skin barrier and antimicrobial defense. Direct LL‑37 supplementation isn’t covered, and boosting LL‑37 could also raise cytokines linked to itch, so monitor skin symptoms and avoid excessive dosing.
Summary
People with eczema have lower blood levels of the antimicrobial peptide LL‑37 and vitamin D. Giving the active form of vitamin D to skin cells boosts LL‑37 production, and both vitamin D and LL‑37 can increase certain immune signals (IL‑31 and oncostatin M) in T‑cells. For healthy folks, keeping vitamin D sufficient may help maintain LL‑37 levels, but the immune effects are complex and not all clearly beneficial.
Abstract
Skin lesions with atopic dermatitis (AD) are associated with dysregulated expression of LL-37 and enhanced expression of IL-22, thymic stromal lymphopoietin (TSLP), IL-25, IL-31, and oncostatin M. Vitamin D3 enhances LL-37 production in keratinocytes. This study aimed to examine the serum levels of LL-37 and vitamin D3 and their regulation of cytokine production in patients with AD. Serum levels of LL-37 and 25-hydroxyvitamin D3 were analyzed by ELISA. The effects of 1,25-dihydroxyvitamin D3 or LL-37 on cytokine production in T cells or keratinocytes were analyzed by ELISA and real-time PCR. Serum levels of LL-37 and 25-hydroxyvitamin D3 were decreased in patients with AD compared to normal donors and were correlated in both groups. Serum levels of LL-37 correlated with those of oncostatin M and IL-31 in normal donors and patients with AD, while 25-hydroxyvitamin D3 levels did so only in normal donors. 1,25-dihydroxyvitamin D3 increased LL-37 production in human keratinocytes and neutrophils. 1,25-dihydroxyvitamin D3 and LL-37 enhanced the oncostatin M and IL-31 production in CD3/28-stimulated T cells, but did not alter IL-25 and TSLP production in TNF-α-stimulated keratinocytes. In CD3/28-stimulated T cells, 1,25-dihydroxyvitamin D3 reduced the IL-22 production, while LL-37 enhanced it. These effects of 1,25-dihydroxyvitamin D3 and LL-37 were suppressed by vitamin D receptor antagonist and pertussis toxin, respectively. Systemic vitamin D3 levels are reduced in patients with AD, which may contribute to decreased systemic LL-37 levels. LL-37 may systemically potentiate the oncostatin M and IL-31 production in normal donors and patients with AD, while vitamin D3 may do so only in normal donors.
Study Information
pubmed
2012
2012-04-10T00:00:00.000Z
10.1111/j.1398-9995.2012.02824.x
63
33